Search results

Title: Review: brain neurobiology of gambling disorder based on rodent models.
Creator: Quintero Garzola, Gabriel C
Abstract/Description: Different literature reviews of gambling disorder (GD) neurobiology have been focused on human studies, others have focused on rodents, and others combined human and rodent studies. The main question of this review was: which are the main neurotransmitters systems and brain structures relevant for GD based on recent rodent studies? This work aims to review the experimental ﬁndings regarding the rodent´s neurobiology of GD. A search in the Pub Med database was set (October 2012–October 2017)...
Show moreDifferent literature reviews of gambling disorder (GD) neurobiology have been focused on human studies, others have focused on rodents, and others combined human and rodent studies. The main question of this review was: which are the main neurotransmitters systems and brain structures relevant for GD based on recent rodent studies? This work aims to review the experimental ﬁndings regarding the rodent´s neurobiology of GD. A search in the Pub Med database was set (October 2012–October 2017) and 162 references were obtained. After screening, 121 references were excluded, and only 41 references remained from the initial output. More, other 25 references were added to complement (introduction section, neuroanatomical descriptions) the principal part of the work. At the end, a total of 66 references remained for the review. The main conclusions are: 1) according to studies that used noninvasive methods for drug administration, some of the neurotransmitters and receptors involved in behaviors related to GD are: muscarinic, N-methyl-D-aspartate (NMDA), cannabinoid receptor 1 (CB1), cannabinoid receptor 2 (CB2), dopamine 2 receptor (D2), dopamine 3 receptor (D3), and dopamine 4 receptor (D4); 2) moreover, there are other neurotransmitters and receptors involved in GD based on studies that use invasive methods of drug administration (eg, brain microinjection); example of these are: serotonin 1A receptor (5-HT1A), noradrenaline receptors, gamma-aminobutyric acid receptor A (GABAA), and gamma-aminobutyric acid receptor B (GABAB); 3) different brain structures are relevant to behaviors linked to GD, like: amygdala (including basolateral amygdala (BLA)), anterior cingulate cortex (ACC), hippocampus, infralimbic area, insular cortex (anterior and rostral agranular), nucleus accumbens (NAc), olfactory tubercle (island of Calleja), orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), prefrontal cortex (PFC) – subcortical network, striatum (ventral) and the subthalamic nucleus (STN); and 4) the search for GD treatments should consider this diversity of receptor/neurotransmitter systems and brain areas.
Show less
Date Issued: 2019-07-02
Identifier: FSU_libsubv1_scholarship_submission_1562679786_1b1febed
Format: Citation

Title: Postsynaptic Fmrp Regulates Synaptogenesis In Vivo In The Developing Cochlear Nucleus.
Creator: Wang, Xiaoyu, Zorio, Diego A. R., Schecterson, Leslayann, Lu, Yong, Wang, Yuan
Abstract/Description: A global loss of the fragile X mental retardation protein (FMRP; encoded by the Fmr1 gene) leads to sensory dysfunction and intellectual disabilities. One underlying mechanism of these phenotypes is structural and functional deficits in synapses. Here, we determined the autonomous function of postsynaptic FMRP in circuit formation, synaptogenesis, and synaptic maturation. In normal cochlea nucleus, presynaptic auditory axons form large axosomatic endbulb synapses on cell bodies of...
Show moreA global loss of the fragile X mental retardation protein (FMRP; encoded by the Fmr1 gene) leads to sensory dysfunction and intellectual disabilities. One underlying mechanism of these phenotypes is structural and functional deficits in synapses. Here, we determined the autonomous function of postsynaptic FMRP in circuit formation, synaptogenesis, and synaptic maturation. In normal cochlea nucleus, presynaptic auditory axons form large axosomatic endbulb synapses on cell bodies of postsynaptic bushy neurons. In ovo electroporation of drug-inducible Fmr1-shRNA constructs produced a mosaicism of FMRP expression in chicken (either sex) bushy neurons, leading to reduced FMRP levels in transfected, but not neighboring nontransfected, neurons. Structural analyses revealed that postsynaptic FMRP reduction led to smaller size and abnormal morphology of individual presynaptic endbulbs at both early and later developmental stages. We further examined whether FMRP reduction affects dendritic development, as a potential mechanism underlying defective endbulb formation. Normally, chicken bushy neurons grow extensive dendrites at early stages and retract these dendrites when endbulbs begin to form. Neurons transfected with Fmr1 shRNA exhibited a remarkable delay in branch retraction, failing to provide necessary somatic surface for timely formation and growth of large endbulbs. Patch-clamp recording verified functional consequences of dendritic and synaptic deficits on neurotransmission, showing smaller amplitudes and slower kinetics of spontaneous and evoked EPSCs. Together, these data demonstrate that proper levels of postsynaptic FMRP are required for timely maturation of somatodendritic morphology, a delay of which may affect synaptogenesis and thus contribute to long-lasting deficits of excitatory synapses.
Show less
Date Issued: 2018-07-18
Identifier: FSU_libsubv1_wos_000439698400004, 10.1523/JNEUROSCI.0665-18.2018
Format: Citation

Title: Selective activation of estrogen receptors, ERα and GPER-1, rapidly decreases food intake in female rats.
Creator: Butler, Michael J, Hildebrandt, Ryan P, Eckel, Lisa A
Abstract/Description: Many of estradiol's behavioral effects are mediated, at least partially, via extra-nuclear estradiol signaling. Here, we investigated whether two estrogen receptor (ER) agonists, targeting ERα and G protein-coupled ER-1 (GPER-1), can promote rapid anorexigenic effects. Food intake was measured in ovariectomized (OVX) rats at 1, 2, 4, and 22 h following subcutaneous (s.c.) injection of an ERα agonist (PPT; 0-200 μg/kg), a GPER-1 agonist (G-1; 0-1600 μg/kg), and a GPER-1 antagonist (G-36; 0-80...
Show moreMany of estradiol's behavioral effects are mediated, at least partially, via extra-nuclear estradiol signaling. Here, we investigated whether two estrogen receptor (ER) agonists, targeting ERα and G protein-coupled ER-1 (GPER-1), can promote rapid anorexigenic effects. Food intake was measured in ovariectomized (OVX) rats at 1, 2, 4, and 22 h following subcutaneous (s.c.) injection of an ERα agonist (PPT; 0-200 μg/kg), a GPER-1 agonist (G-1; 0-1600 μg/kg), and a GPER-1 antagonist (G-36; 0-80 μg/kg). To investigate possible cross-talk between ERα and GPER-1, we examined whether GPER-1 blockade affects the anorexigenic effect of PPT. Feeding was monitored in OVX rats that received s.c. injections of vehicle or 40 μg/kg G-36 followed 30 min later by s.c. injections of vehicle or 200 μg/kg PPT. Selective activation of ERα and GPER-1 alone decreased food intake within 1 h of drug treatment, and feeding remained suppressed for 22 h following PPT treatment and 4 h following G-1 treatment. Acute administration of G-36 alone did not suppress feeding at any time point. Blockade of GPER-1 attenuated PPT's rapid (within 1 h) anorexigenic effect, but did not modulate PPT's ability to suppress food intake at 2, 4 and 22 h. These findings demonstrate that selective activation of ERα produces a rapid (within 1 h) decrease in food intake that is best explained by a non-genomic signaling pathway and thus implicates the involvement of extra-nuclear ERα. Our findings also provide evidence that activation of GPER-1 is both sufficient to suppress feeding and necessary for PPT's rapid anorexigenic effect.
Show less
Date Issued: 2018-07-01
Identifier: FSU_pmch_29807036, 10.1016/j.yhbeh.2018.05.018, PMC6076327, 29807036, 29807036, S0018-506X(18)30012-6
Format: Citation

Title: Diverse Intrinsic Properties Shape Functional Phenotype Of Low-frequency Neurons In The Auditory Brainstem.
Creator: Hong, Hui, Wang, Xiaoyu, Lu, Ting, Zorio, Diego A. R., Wang, Yuan, Sanchez, Jason Tait
Abstract/Description: In the auditory system, tonotopy is the spatial arrangement of where sounds of different frequencies are processed. Defined by the organization of neurons and their inputs, tonotopy emphasizes distinctions in neuronal structure and function across topographic gradients and is a common feature shared among vertebrates. In this study we characterized action potential firing patterns and ion channel properties from neurons located in the extremely low-frequency region of the chicken nucleus...
Show moreIn the auditory system, tonotopy is the spatial arrangement of where sounds of different frequencies are processed. Defined by the organization of neurons and their inputs, tonotopy emphasizes distinctions in neuronal structure and function across topographic gradients and is a common feature shared among vertebrates. In this study we characterized action potential firing patterns and ion channel properties from neurons located in the extremely low-frequency region of the chicken nucleus magnocellularis (NM), an auditory brainstem structure. We found that NM neurons responsible for encoding the lowest sound frequencies (termed NMc neurons) have enhanced excitability and fired bursts of action potentials to sinusoidal inputs <= 10 Hz; a distinct firing pattern compared to higher-frequency neurons. This response property was due to lower amounts of voltage dependent potassium (K-v) conductances, unique combination of K-v subunits and specialized sodium (Na-v) channel properties. Particularly, NMc neurons had significantly lower K(v)1 and K(v)3 currents, but higher K(v)2current. NMc neurons also showed larger and faster transient Nav current (I-NaT) with different voltage dependence of inactivation from higher-frequency neurons. In contrast, significantly smaller resurgent sodium current (I-NaR) was present in NMc with kinetics and voltage dependence that differed from higher-frequency neurons. Immunohistochemistry showed expression of Na(v)1.6 channel subtypes across the tonotopic axis. However, various immunoreactive patterns were observed between regions, likely underlying some tonotopic differences in I-N(aT) and I-NaR. Finally, using pharmacology and computational modeling, we concluded that K(v)3, K(v)2 channels and I-NaR work synergistically to regulate burst firing in NMc.
Show less
Date Issued: 2018-06-26
Identifier: FSU_libsubv1_wos_000436338700001, 10.3389/fncel.2018.00175
Format: Citation

Title: Diverse Intrinsic Properties Shape Functional Phenotype of Low-Frequency Neurons in the Auditory Brainstem.
Creator: Hong, Hui, Wang, Xiaoyu, Lu, Ting, Zorio, Diego A R, Wang, Yuan, Sanchez, Jason Tait
Abstract/Description: In the auditory system, tonotopy is the spatial arrangement of where sounds of different frequencies are processed. Defined by the organization of neurons and their inputs, tonotopy emphasizes distinctions in neuronal structure and function across topographic gradients and is a common feature shared among vertebrates. In this study we characterized action potential firing patterns and ion channel properties from neurons located in the extremely low-frequency region of the chicken nucleus...
Show moreIn the auditory system, tonotopy is the spatial arrangement of where sounds of different frequencies are processed. Defined by the organization of neurons and their inputs, tonotopy emphasizes distinctions in neuronal structure and function across topographic gradients and is a common feature shared among vertebrates. In this study we characterized action potential firing patterns and ion channel properties from neurons located in the extremely low-frequency region of the chicken nucleus magnocellularis (NM), an auditory brainstem structure. We found that NM neurons responsible for encoding the lowest sound frequencies (termed NMc neurons) have enhanced excitability and fired bursts of action potentials to sinusoidal inputs ≤10 Hz; a distinct firing pattern compared to higher-frequency neurons. This response property was due to lower amounts of voltage dependent potassium (K) conductances, unique combination of K subunits and specialized sodium (Na) channel properties. Particularly, NMc neurons had significantly lower K1 and K3 currents, but higher K2 current. NMc neurons also showed larger and faster transient Na current () with different voltage dependence of inactivation from higher-frequency neurons. In contrast, significantly smaller resurgent sodium current () was present in NMc with kinetics and voltage dependence that differed from higher-frequency neurons. Immunohistochemistry showed expression of Na1.6 channel subtypes across the tonotopic axis. However, various immunoreactive patterns were observed between regions, likely underlying some tonotopic differences in and . Finally, using pharmacology and computational modeling, we concluded that K3, K2 channels and work synergistically to regulate burst firing in NMc.
Show less
Date Issued: 2018-06-26
Identifier: FSU_pmch_29997479, 10.3389/fncel.2018.00175, PMC6028565, 29997479, 29997479
Format: Citation

Title: New horizons for future research - Critical issues to consider for maximizing research excellence and impact.
Creator: Langhans, Wolfgang, Adan, Roger, Arnold, Myrtha, Banks, William A, Card, J Patrick, Dailey, Megan J, Daniels, Derek, de Kloet, Annette D, de Lartigue, Guillaume, Dickson,...
Show moreLanghans, Wolfgang, Adan, Roger, Arnold, Myrtha, Banks, William A, Card, J Patrick, Dailey, Megan J, Daniels, Derek, de Kloet, Annette D, de Lartigue, Guillaume, Dickson, Suzanne, Fedele, Shahana, Grill, Harvey J, Jansson, John-Olov, Kaufman, Sharon, Kolar, Grant, Krause, Eric, Lee, Shin J, Le Foll, Christelle, Levin, Barry E, Lutz, Thomas A, Mansouri, Abdelhak, Moran, Timothy H, Pacheco-López, Gustavo, Ramachandran, Deepti, Raybould, Helen, Rinaman, Linda, Samson, Willis K, Sanchez-Watts, Graciela, Seeley, Randy J, Skibicka, Karolina P, Small, Dana, Spector, Alan C, Tamashiro, Kellie L, Templeton, Brian, Trapp, Stefan, Tso, Patrick, Watts, Alan G, Weissfeld, Nadja, Williams, Diana, Wolfrum, Christian, Yosten, Gina, Woods, Stephen C
Show less
Date Issued: 2018-05-12
Identifier: FSU_pmch_29886182, 10.1016/j.molmet.2018.05.007, PMC6034110, 29886182, 29886182, S2212-8778(18)30363-6
Format: Citation

Title: mTOR signaling regulates central and peripheral circadian clock function.
Creator: Ramanathan, Chidambaram, Kathale, Nimish D, Liu, Dong, Lee, Choogon, Freeman, David A, Hogenesch, John B, Cao, Ruifeng, Liu, Andrew C
Abstract/Description: The circadian clock coordinates physiology and metabolism. mTOR (mammalian/mechanistic target of rapamycin) is a major intracellular sensor that integrates nutrient and energy status to regulate protein synthesis, metabolism, and cell growth. Previous studies have identified a key role for mTOR in regulating photic entrainment and synchrony of the central circadian clock in the suprachiasmatic nucleus (SCN). Given that mTOR activities exhibit robust circadian oscillations in a variety of...
Show moreThe circadian clock coordinates physiology and metabolism. mTOR (mammalian/mechanistic target of rapamycin) is a major intracellular sensor that integrates nutrient and energy status to regulate protein synthesis, metabolism, and cell growth. Previous studies have identified a key role for mTOR in regulating photic entrainment and synchrony of the central circadian clock in the suprachiasmatic nucleus (SCN). Given that mTOR activities exhibit robust circadian oscillations in a variety of tissues and cells including the SCN, here we continued to investigate the role of mTOR in orchestrating autonomous clock functions in central and peripheral circadian oscillators. Using a combination of genetic and pharmacological approaches we show that mTOR regulates intrinsic clock properties including period and amplitude. In peripheral clock models of hepatocytes and adipocytes, mTOR inhibition lengthens period and dampens amplitude, whereas mTOR activation shortens period and augments amplitude. Constitutive activation of mTOR in Tsc2-/-fibroblasts elevates levels of core clock proteins, including CRY1, BMAL1 and CLOCK. Serum stimulation induces CRY1 upregulation in fibroblasts in an mTOR-dependent but Bmal1- and Period-independent manner. Consistent with results from cellular clock models, mTOR perturbation also regulates period and amplitude in the ex vivo SCN and liver clocks. Further, mTOR heterozygous mice show lengthened circadian period of locomotor activity in both constant darkness and constant light. Together, these results support a significant role for mTOR in circadian timekeeping and in linking metabolic states to circadian clock functions.
Show less
Date Issued: 2018-05-11
Identifier: FSU_pmch_29750810, 10.1371/journal.pgen.1007369, PMC5965903, 29750810, 29750810, PGENETICS-D-17-02178
Format: Citation

Title: Mtor Signaling Regulates Central And Peripheral Circadian Clock Function.
Creator: Ramanathan, Chidambaram, Kathale, Nimish D., Liu, Dong, Lee, Choogon, Freeman, David A., Hogenesch, John B., Cao, Ruifeng, Liu, Andrew C.
Abstract/Description: The circadian clock coordinates physiology and metabolism. mTOR (mammalianmechanistic target of rapamycin) is a major intracellular sensor that integrates nutrient and energy status to regulate protein synthesis, metabolism, and cell growth. Previous studies have identified a key role for mTOR in regulating photic entrainment and synchrony of the central circadian clock in the suprachiasmatic nucleus (SCN). Given that mTOR activities exhibit robust circadian oscillations in a variety of...
Show moreThe circadian clock coordinates physiology and metabolism. mTOR (mammalianmechanistic target of rapamycin) is a major intracellular sensor that integrates nutrient and energy status to regulate protein synthesis, metabolism, and cell growth. Previous studies have identified a key role for mTOR in regulating photic entrainment and synchrony of the central circadian clock in the suprachiasmatic nucleus (SCN). Given that mTOR activities exhibit robust circadian oscillations in a variety of tissues and cells including the SCN, here we continued to investigate the role of mTOR in orchestrating autonomous clock functions in central and peripheral circadian oscillators. Using a combination of genetic and pharmacological approaches we show that mTOR regulates intrinsic clock properties including period and amplitude. In peripheral clock models of hepatocytes and adipocytes, mTOR inhibition lengthens period and dampens amplitude, whereas mTOR activation shortens period and augments amplitude. Constitutive activation of mTOR in Tsc2(-/-)fibroblasts elevates levels of core clock proteins, including CRY1, BMAL1 and CLOCK. Serum stimulation induces CRY1 upregulation in fibroblasts in an mTOR-dependent but Bmal1- and Period-independent manner. Consistent with results from cellular clock models, mTOR perturbation also regulates period and amplitude in the ex vivo SCN and liver clocks. Further, mTOR heterozygous mice show lengthened circadian period of locomotor activity in both constant darkness and constant light. Together, these results support a significant role for mTOR in circadian timekeeping and in linking metabolic states to circadian clock functions.
Show less
Date Issued: 2018-05-01
Identifier: FSU_libsubv1_wos_000434016500019, 10.1371/journal.pgen.1007369
Format: Citation

Title: Elevated Anxiety and Impaired Attention in Super-Smeller, Kv1.3 Knockout Mice.
Creator: Huang, Zhenbo, Hoffman, Carlie A, Chelette, Brandon M, Thiebaud, Nicolas, Fadool, Debra A
Abstract/Description: It has long been recognized that olfaction and emotion are linked. While chemosensory research using both human and rodent models have indicated a change in emotion can contribute to olfactory dysfunction, there are few studies addressing the contribution of olfaction to a modulation in emotion. In mice, olfactory deficits have been linked with heightened anxiety levels, suggesting that there could be an inverse relationship between olfaction and anxiety. Furthermore, increased anxiety is...
Show moreIt has long been recognized that olfaction and emotion are linked. While chemosensory research using both human and rodent models have indicated a change in emotion can contribute to olfactory dysfunction, there are few studies addressing the contribution of olfaction to a modulation in emotion. In mice, olfactory deficits have been linked with heightened anxiety levels, suggesting that there could be an inverse relationship between olfaction and anxiety. Furthermore, increased anxiety is often co-morbid with psychiatric conditions such as attention disorders. Our study aimed to investigate the roles of olfaction in modulating anxiety. Voltage-gated potassium ion channel Kv1.3 knockout mice (Kv1.3-/-), which have heightened olfaction, and wild-type (WT) mice were examined for anxiety-like behaviors using marble burying (MB), light-dark box (LDB) and elevated-plus maze (EPM) tests. Because Kv1.3-/- mice have increased locomotor activity, inattentive and hyperactive behaviors were quantified for both genotypes. Kv1.3-/- mice showed increased anxiety levels compared to their WT counterparts and administration of methylphenidate (MPH) via oral gavage alleviated their increased anxiety. Object-based attention testing indicated young and older Kv1.3-/- mice had attention deficits and treatment with MPH also ameliorated this condition. Locomotor testing through use of a metabolic chamber indicated that Kv1.3-/- mice were not significantly hyperactive and MPH treatment failed to modify this activity. Our data suggest that heightened olfaction does not necessarily lead to decreased anxiety levels, and that Kv1.3-/- mice may have behaviors associated with inattentiveness.
Show less
Date Issued: 2018-03-19
Identifier: FSU_pmch_29615878, 10.3389/fnbeh.2018.00049, PMC5867313, 29615878, 29615878
Format: Citation

Title: Synchrotron-generated microbeams induce hippocampal transections in rats.
Creator: Fardone, Erminia, Pouyatos, Benoît, Bräuer-Krisch, Elke, Bartzsch, Stefan, Mathieu, Hervè, Requardt, Herwig, Bucci, Domenico, Barbone, Giacomo, Coan, Paola, Battaglia, Giuseppe,...
Show moreFardone, Erminia, Pouyatos, Benoît, Bräuer-Krisch, Elke, Bartzsch, Stefan, Mathieu, Hervè, Requardt, Herwig, Bucci, Domenico, Barbone, Giacomo, Coan, Paola, Battaglia, Giuseppe, Le Duc, Geraldine, Bravin, Alberto, Romanelli, Pantaleo
Show less
Abstract/Description: Synchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the...
Show moreSynchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the hippocampus of healthy rats. An array of parallel microbeams carrying an incident dose of 600 Gy was delivered to the rat hippocampus. Immunohistochemistry of phosphorylated γ-H2AX showed cell death along the microbeam irradiation paths in rats 48 hours after irradiation. No evident behavioral or neurological deficits were observed during the 3-month period of observation. MR imaging showed no signs of radio-induced edema or radionecrosis 3 months after irradiation. Histological analysis showed a very well preserved hippocampal cytoarchitecture and confirmed the presence of clear-cut microscopic transections across the hippocampus. These data support the use of synchrotron-generated microbeams as a novel tool to slice the hippocampus of living rats in a minimally invasive way, providing (i) a novel experimental model to study hippocampal function and (ii) a new treatment tool for patients affected by refractory epilepsy induced by mesial temporal sclerosis.
Show less
Date Issued: 2018-01-09
Identifier: FSU_pmch_29317649, 10.1038/s41598-017-18000-x, PMC5760574, 29317649, 29317649, 10.1038/s41598-017-18000-x
Format: Citation

Title: Rat sensorimotor cortex tolerance to parallel transections induced by synchrotron-generated X-ray microbeams.
Creator: Fardone, Erminia, Bravin, Alberto, Conti, Alfredo, Bräuer-Krisch, Elke, Requardt, Herwig, Bucci, Domenico, Le Duc, Geraldine, Battaglia, Giuseppe, Romanelli, Pantaleo
Abstract/Description: Microbeam radiation therapy is a novel preclinical technique, which uses synchrotron-generated X-rays for the treatment of brain tumours and drug-resistant epilepsies. In order to safely translate this approach to humans, a more in-depth knowledge of the long-term radiobiology of microbeams in healthy tissues is required. We report here the result of the characterization of the rat sensorimotor cortex tolerance to microradiosurgical parallel transections. Healthy adult male Wistar rats...
Show moreMicrobeam radiation therapy is a novel preclinical technique, which uses synchrotron-generated X-rays for the treatment of brain tumours and drug-resistant epilepsies. In order to safely translate this approach to humans, a more in-depth knowledge of the long-term radiobiology of microbeams in healthy tissues is required. We report here the result of the characterization of the rat sensorimotor cortex tolerance to microradiosurgical parallel transections. Healthy adult male Wistar rats underwent irradiation with arrays of parallel microbeams. Beam thickness, spacing and incident dose were 100 or 600 µm, 400 or 1200 µm and 360 or 150 Gy, respectively. Motor performance was carried over a 3-month period. Three months after irradiation rats were sacrificed to evaluate the effects of irradiation on brain tissues by histology and immunohistochemistry. Microbeam irradiation of sensorimotor cortex did not affect weight gain and motor performance. No gross signs of paralysis or paresis were also observed. The cortical architecture was not altered, despite the presence of cell death along the irradiation path. Reactive gliosis was evident in the microbeam path of rats irradiated with 150 Gy, whereas no increase was observed in rats irradiated with 360 Gy.
Show less
Date Issued: 2017-10-30
Identifier: FSU_pmch_29085040, 10.1038/s41598-017-14757-3, PMC5662592, 29085040, 29085040, 10.1038/s41598-017-14757-3
Format: Citation

Title: Neuronal Intrinsic Physiology Changes During Development of a Learned Behavior.
Creator: Ross, Matthew T, Flores, Diana, Bertram, Richard, Johnson, Frank, Hyson, Richard L
Abstract/Description: Juvenile male zebra finches learn their songs over distinct auditory and sensorimotor stages, the former requiring exposure to an adult tutor song pattern. The cortical premotor nucleus HVC (acronym is name) plays a necessary role in both learning stages, as well as the production of adult song. Consistent with neural network models where synaptic plasticity mediates developmental forms of learning, exposure to tutor song drives changes in the turnover, density, and morphology of HVC synapses...
Show moreJuvenile male zebra finches learn their songs over distinct auditory and sensorimotor stages, the former requiring exposure to an adult tutor song pattern. The cortical premotor nucleus HVC (acronym is name) plays a necessary role in both learning stages, as well as the production of adult song. Consistent with neural network models where synaptic plasticity mediates developmental forms of learning, exposure to tutor song drives changes in the turnover, density, and morphology of HVC synapses during vocal development. A network's output, however, is also influenced by the intrinsic properties (e.g., ion channels) of the component neurons, which could change over development. Here, we use patch clamp recordings to show cell-type-specific changes in the intrinsic physiology of HVC projection neurons as a function of vocal development. Developmental changes in HVC neurons that project to the basal ganglia include an increased voltage sag response to hyperpolarizing currents and an increased rebound depolarization following hyperpolarization. Developmental changes in HVC neurons that project to vocal-motor cortex include a decreased resting membrane potential and an increased spike amplitude. HVC interneurons, however, show a relatively stable range of intrinsic features across vocal development. We used mathematical models to deduce possible changes in ionic currents that underlie the physiological changes and to show that the magnitude of the observed changes could alter HVC circuit function. The results demonstrate developmental plasticity in the intrinsic physiology of HVC projection neurons and suggest that intrinsic plasticity may have a role in the process of song learning.
Show less
Date Issued: 2017-10-20
Identifier: FSU_pmch_29062887, 10.1523/ENEURO.0297-17.2017, PMC5649544, 29062887, 29062887, eN-NWR-0297-17
Format: Citation

Title: 3'-UTR and microRNA-24 regulate circadian rhythms by repressing PERIOD2 protein accumulation.
Creator: Yoo, Seung-Hee, Kojima, Shihoko, Shimomura, Kazuhiro, Koike, Nobuya, Buhr, Ethan D, Furukawa, Tadashi, Ko, Caroline H, Gloston, Gabrielle, Ayoub, Christopher, Nohara, Kazunari,...
Show moreYoo, Seung-Hee, Kojima, Shihoko, Shimomura, Kazuhiro, Koike, Nobuya, Buhr, Ethan D, Furukawa, Tadashi, Ko, Caroline H, Gloston, Gabrielle, Ayoub, Christopher, Nohara, Kazunari, Reyes, Bryan A, Tsuchiya, Yoshiki, Yoo, Ook-Joon, Yagita, Kazuhiro, Lee, Choogon, Chen, Zheng, Yamazaki, Shin, Green, Carla B, Takahashi, Joseph S
Show less
Abstract/Description: We previously created two PER2::LUCIFERASE (PER2::LUC) circadian reporter knockin mice that differ only in the 3'-UTR region: , which retains the endogenous 3'-UTR and , where the endogenous 3'-UTR was replaced by an SV40 late poly(A) signal. To delineate the in vivo functions of 3'-UTR, we analyzed circadian rhythms of mice. Interestingly, mice displayed more than threefold stronger amplitude in bioluminescence rhythms than mice, and also exhibited lengthened free-running periods (∼24.0 h),...
Show moreWe previously created two PER2::LUCIFERASE (PER2::LUC) circadian reporter knockin mice that differ only in the 3'-UTR region: , which retains the endogenous 3'-UTR and , where the endogenous 3'-UTR was replaced by an SV40 late poly(A) signal. To delineate the in vivo functions of 3'-UTR, we analyzed circadian rhythms of mice. Interestingly, mice displayed more than threefold stronger amplitude in bioluminescence rhythms than mice, and also exhibited lengthened free-running periods (∼24.0 h), greater phase delays following light pulse, and enhanced temperature compensation relative to Analysis of the 3'-UTR sequence revealed that miR-24, and to a lesser degree miR-30, suppressed PER2 protein translation, and the reversal of this inhibition in augmented PER2::LUC protein level and oscillatory amplitude. Interestingly, mRNA and protein oscillatory amplitude as well as CRY1 protein oscillation were increased in mice, suggesting rhythmic overexpression of PER2 enhances expression of and other core clock genes. Together, these studies provide important mechanistic insights into the regulatory roles of 3'-UTR, miR-24, and PER2 in expression and core clock function.
Show less
Date Issued: 2017-10-17
Identifier: FSU_pmch_28973913, 10.1073/pnas.1706611114, PMC5651750, 28973913, 28973913, 1706611114
Format: Citation

Title: Proteomic analyses of nucleus laminaris identified candidate targets of the fragile X mental retardation protein.
Creator: Sakano, Hitomi, Zorio, Diego A R, Wang, Xiaoyu, Ting, Ying S, Noble, William S, MacCoss, Michael J, Rubel, Edwin W, Wang, Yuan
Abstract/Description: The avian nucleus laminaris (NL) is a brainstem nucleus necessary for binaural processing, analogous in structure and function to the mammalian medial superior olive. In chickens (Gallus gallus), NL is a well-studied model system for activity-dependent neural plasticity. Its neurons have bipolar extension of dendrites, which receive segregated inputs from two ears and display rapid and compartment-specific reorganization in response to unilateral changes in auditory input. More recently,...
Show moreThe avian nucleus laminaris (NL) is a brainstem nucleus necessary for binaural processing, analogous in structure and function to the mammalian medial superior olive. In chickens (Gallus gallus), NL is a well-studied model system for activity-dependent neural plasticity. Its neurons have bipolar extension of dendrites, which receive segregated inputs from two ears and display rapid and compartment-specific reorganization in response to unilateral changes in auditory input. More recently, fragile X mental retardation protein (FMRP), an RNA-binding protein that regulates local protein translation, has been shown to be enriched in NL dendrites, suggesting its potential role in the structural dynamics of these dendrites. To explore the molecular role of FMRP in this nucleus, we performed proteomic analysis of NL, using micro laser capture and liquid chromatography tandem mass spectrometry. We identified 657 proteins, greatly represented in pathways involved in mitochondria, translation and metabolism, consistent with high levels of activity of NL neurons. Of these, 94 are potential FMRP targets, by comparative analysis with previously proposed FMRP targets in mammals. These proteins are enriched in pathways involved in cellular growth, cellular trafficking and transmembrane transport. Immunocytochemistry verified the dendritic localization of several proteins in NL. Furthermore, we confirmed the direct interaction of FMRP with one candidate, RhoC, by in vitro RNA binding assays. In summary, we provide a database of highly expressed proteins in NL and in particular a list of potential FMRP targets, with the goal of facilitating molecular characterization of FMRP signaling in future studies.
Show less
Date Issued: 2017-10-15
Identifier: FSU_pmch_28685837, 10.1002/cne.24281, PMC5564178, 28685837, 28685837
Format: Citation

Title: Aging and circadian dysfunction increase alcohol sensitivity and exacerbate mortality in Drosophila melanogaster.
Creator: De Nobrega, Aliza K, Mellers, Alana P, Lyons, Lisa C
Abstract/Description: Alcohol abuse is a rising problem in middle-aged and older individuals resulting in serious health, family and economic consequences. Effective treatment necessitates the identification of factors influencing alcohol toxicity with aging. We investigated the interaction between aging, alcohol toxicity and circadian function using Drosophila as a model system. We found as wild type flies age, sensitivity to alcohol increases and circadian regulation of alcohol-induced behaviors weakens....
Show moreAlcohol abuse is a rising problem in middle-aged and older individuals resulting in serious health, family and economic consequences. Effective treatment necessitates the identification of factors influencing alcohol toxicity with aging. We investigated the interaction between aging, alcohol toxicity and circadian function using Drosophila as a model system. We found as wild type flies age, sensitivity to alcohol increases and circadian regulation of alcohol-induced behaviors weakens. Decreased circadian modulation is correlated with significantly greater alcohol sensitivity during the subjective day. The circadian clock modulates alcohol-induced mortality in younger flies with increased mortality following alcohol exposure at night. Older flies exhibit significantly longer recovery times following alcohol-induced sedation and increased mortality following binge-like or chronic alcohol exposure. Flies rendered arrhythmic either genetically or environmentally exhibit significantly increased alcohol sensitivity, longer recovery times and increased mortality. We hypothesize that the circadian clock phase specifically buffers behavioral and cellular alcohol sensitivity with this protection diminishing as the circadian clock weakens with age.
Show less
Date Issued: 2017-10-15
Identifier: FSU_pmch_28750752, 10.1016/j.exger.2017.07.014, PMC6158789, 28750752, 28750752, S0531-5565(17)30055-4
Format: Citation

Title: Heterogeneous organization and connectivity of the chicken auditory thalamus (Gallus gallus).
Creator: Wang, Yuan, Zorio, Diego A R, Karten, Harvey J
Abstract/Description: The auditory ascending system contains parallel pathways in vertebrate brains. In chickens (Gallus gallus), three pathways arise from nucleus laminaris (NL), nucleus angularis (NA), and regio intermedius (RI) in the brainstem, innervating three subdivisions of the nucleus mesencephalicus lateralis pars dorsalis (MLd) in the midbrain. The current study reveals the segregation of these pathways in their subsequent projections to the nucleus ovoidalis (Ov) in the thalamus. Based on...
Show moreThe auditory ascending system contains parallel pathways in vertebrate brains. In chickens (Gallus gallus), three pathways arise from nucleus laminaris (NL), nucleus angularis (NA), and regio intermedius (RI) in the brainstem, innervating three subdivisions of the nucleus mesencephalicus lateralis pars dorsalis (MLd) in the midbrain. The current study reveals the segregation of these pathways in their subsequent projections to the nucleus ovoidalis (Ov) in the thalamus. Based on cytoarchitecture and myelin distribution, we identified seven Ov subregions, including five neuronal clusters within the Ov proper, the nucleus semilunaris parovoidalis (SPO), and the circum-ovoidalis (cOv). Immunocytochemistry further revealed that a ventromedial cluster of the Ov proper (Ovvm) contains unique cell types expressing α8 subunit nicotinic acetylcholine receptor, while SPO and cOv are characterized with expression of calcitonin-gene-related peptide and cholecystokinin. Tract tracing studies demonstrated that Ovvm is a major target of the NL-recipient zone of MLd, while the RI-recipient zone of MLd predominantly projects to a ventrolateral cluster of the Ov proper. Afferent inputs to the remaining regions of the Ov proper mostly arise from the NA-recipient zone of MLd. SPO and cOv receive a projection from the surrounding areas of MLd, named the nucleus intercollicularis. Importantly, the Ov proper, SPO and cOv all project to the Field L2 in the forebrain, the avian auditory cortex. Taken together, these results demonstrate that the avian auditory thalamus is a structurally and functionally heterogeneous structure, implicating an important role in generating novel representations for specific acoustic features.
Show less
Date Issued: 2017-10-01
Identifier: FSU_pmch_28614906, 10.1002/cne.24262, PMC5558206, 28614906, 28614906
Format: Citation

Title: Thirst Increases Chorda Tympani Responses to Sodium Chloride.
Creator: Mast, Thomas G, Breza, Joseph M, Contreras, Robert J
Abstract/Description: In nature, water is present as a low-salt solution, thus we hypothesized that thirst would increase taste responses to low-salt solutions. We investigated the effect of thirst on the 2 different salt detection mechanisms present in the rat chorda tympani (CT) nerve. The first mechanism is dependent upon the epithelial sodium channel (ENaC), is blocked by benzamil, and is specific to the cation sodium. The second mechanism, while undefined, is independent of ENaC, and detects multiple cations....
Show moreIn nature, water is present as a low-salt solution, thus we hypothesized that thirst would increase taste responses to low-salt solutions. We investigated the effect of thirst on the 2 different salt detection mechanisms present in the rat chorda tympani (CT) nerve. The first mechanism is dependent upon the epithelial sodium channel (ENaC), is blocked by benzamil, and is specific to the cation sodium. The second mechanism, while undefined, is independent of ENaC, and detects multiple cations. We expected thirst to increase benzamil-sensitive sodium responses due to mechanistically increasing the benzamil-sensitive ENaC. We recorded CT whole-nerve electrophysiological responses to lingual application of NaCl, KCl (30, 75, 150, 300, 500, and 600 mM), and imitation rainwater in both control and 24-h water-restricted male rats. NaCl solutions were presented in artificial saliva before and after lingual application of 5µM benzamil. Water restriction significantly increased the integrated CT responses to NaCl but not to KCl or imitation rainwater. Consistent with our hypothesis, only the benzamil-sensitive, and not the benzamil-insensitive, CT sodium response significantly increased. Additionally, CT responses to salt were recorded following induction of either osmotic or volemic thirst. Both thirsts significantly enhanced the integrated CT responses to NaCl and KCl, but not imitation rainwater. Interestingly, osmotic and volemic thirsts increased CT responses by increasing both the benzamil-sensitive and benzamil-insensitive CT sodium responses. We propose that thirst increases the sensitivity of the CT nerve to sodium.
Show less
Date Issued: 2017-10-01
Identifier: FSU_pmch_28981824, 10.1093/chemse/bjx052, PMC5863560, 28981824, 28981824, 4083245
Format: Citation

Title: Effects of pair bonding on parental behavior and dopamine activity in the nucleus accumbens in male prairie voles.
Creator: Lei, K, Liu, Y, Smith, A S, Lonstein, J S, Wang, Z
Abstract/Description: Male parental care is a vital behavior for the development as well as the physical and mental well-being of the young. However, little is known about the neurochemical regulation of male parental behavior, mainly due to the lack of appropriate animal models. In this study, we used the socially monogamous male prairie vole (Microtus ochrogaster) to investigate the effect of pair-bonding experience on paternal behavior and dopamine (DA) signaling in the nucleus accumbens (NAcc) in the brain. We...
Show moreMale parental care is a vital behavior for the development as well as the physical and mental well-being of the young. However, little is known about the neurochemical regulation of male parental behavior, mainly due to the lack of appropriate animal models. In this study, we used the socially monogamous male prairie vole (Microtus ochrogaster) to investigate the effect of pair-bonding experience on paternal behavior and dopamine (DA) signaling in the nucleus accumbens (NAcc) in the brain. We compared sexually naïve males with males that were pair bonded with a female for two weeks. Our data showed that pair-bonded males displayed enhanced paternal behavior, particularly in pup licking/grooming, associated with increased DA type-1 receptor (D1R) protein expression in the NAcc, compared to sexually naïve males. Site-specific brain microdialysis revealed a significant, but transient, increase in DA release in the NAcc associated with pup exposure in both groups of the males. Further, pharmacological blockade of D1R in the NAcc decreased pup licking/grooming in the pair-bonded males. Together, our data demonstrate that pair-bonding experience with a female facilitated male parental behavior via NAcc D1R mediation in male prairie voles.
Show less
Date Issued: 2017-10-01
Identifier: FSU_pmch_28858415, 10.1111/ejn.13673, PMC5624856, 28858415, 28858415
Format: Citation

Title: The Effects of GABAergic Polarity Changes on Episodic Neural Network Activity in Developing Neural Systems.
Creator: Blanco, Wilfredo, Bertram, Richard, Tabak, Joël
Abstract/Description: Early in development, neural systems have primarily excitatory coupling, where even GABAergic synapses are excitatory. Many of these systems exhibit spontaneous episodes of activity that have been characterized through both experimental and computational studies. As development progress the neural system goes through many changes, including synaptic remodeling, intrinsic plasticity in the ion channel expression, and a transformation of GABAergic synapses from excitatory to inhibitory. What...
Show moreEarly in development, neural systems have primarily excitatory coupling, where even GABAergic synapses are excitatory. Many of these systems exhibit spontaneous episodes of activity that have been characterized through both experimental and computational studies. As development progress the neural system goes through many changes, including synaptic remodeling, intrinsic plasticity in the ion channel expression, and a transformation of GABAergic synapses from excitatory to inhibitory. What effect each of these, and other, changes have on the network behavior is hard to know from experimental studies since they all happen in parallel. One advantage of a computational approach is that one has the ability to study developmental changes in isolation. Here, we examine the effects of GABAergic synapse polarity change on the spontaneous activity of both a mean field and a neural network model that has both glutamatergic and GABAergic coupling, representative of a developing neural network. We find some intuitive behavioral changes as the GABAergic neurons go from excitatory to inhibitory, shared by both models, such as a decrease in the duration of episodes. We also find some paradoxical changes in the activity that are only present in the neural network model. In particular, we find that during early development the inter-episode durations become longer on average, while later in development they become shorter. In addressing this unexpected finding, we uncover a priming effect that is particularly important for a small subset of neurons, called the "intermediate neurons." We characterize these neurons and demonstrate why they are crucial to episode initiation, and why the paradoxical behavioral change result from priming of these neurons. The study illustrates how even arguably the simplest of developmental changes that occurs in neural systems can present non-intuitive behaviors. It also makes predictions about neural network behavioral changes that occur during development that may be observable even in actual neural systems where these changes are convoluted with changes in synaptic connectivity and intrinsic neural plasticity.
Show less
Date Issued: 2017-09-29
Identifier: FSU_pmch_29085291, 10.3389/fncom.2017.00088, PMC5649201, 29085291, 29085291
Format: Citation

Title: Laminar Organization of Encoding and Memory Reactivation in the Parietal Cortex.
Creator: Wilber, Aaron A, Skelin, Ivan, Wu, Wei, McNaughton, Bruce L
Abstract/Description: Egocentric neural coding has been observed in parietal cortex (PC), but its topographical and laminar organization is not well characterized. We used multi-site recording to look for evidence of local clustering and laminar consistency of linear and angular velocity encoding in multi-neuronal spiking activity (MUA) and in the high-frequency (300-900 Hz) component of the local field potential (HF-LFP), believed to reflect local spiking activity. Rats were trained to run many trials on a large...
Show moreEgocentric neural coding has been observed in parietal cortex (PC), but its topographical and laminar organization is not well characterized. We used multi-site recording to look for evidence of local clustering and laminar consistency of linear and angular velocity encoding in multi-neuronal spiking activity (MUA) and in the high-frequency (300-900 Hz) component of the local field potential (HF-LFP), believed to reflect local spiking activity. Rats were trained to run many trials on a large circular platform, either to LED-cued goal locations or as a spatial sequence from memory. Tuning to specific self-motion states was observed and exhibited distinct cortical depth-invariant coding properties. These patterns of collective local and laminar activation during behavior were reactivated in compressed form during post-experience sleep and temporally coupled to cortical delta waves and hippocampal sharp-wave ripples. Thus, PC neuron motion encoding is consistent across cortical laminae, and this consistency is maintained during memory reactivation.
Show less
Date Issued: 2017-09-13
Identifier: FSU_pmch_28910623, 10.1016/j.neuron.2017.08.033, PMC5679317, 28910623, 28910623, S0896-6273(17)30748-1
Format: Citation

Title: Liraglutide suppression of caloric intake competes with the intake-promoting effects of a palatable cafeteria diet, but does not impact food or macronutrient selection.
Creator: Hyde, Kellie M, Blonde, Ginger D, le Roux, Carel W, Spector, Alan C
Abstract/Description: Liraglutide, a Glucagon-Like Peptide-1 (GLP-1) receptor agonist, is used as a treatment for Type 2 diabetes mellitus and obesity because it improves glycemia and decreases food intake. Here, we tested whether chronic activation of the GLP-1 receptor system with liraglutide would induce decreases in intake accompanied by changes in proportional food or macronutrient intake similar to those seen following RYGB in rats when a variety of palatable food options are available. A "cafeteria diet"...
Show moreLiraglutide, a Glucagon-Like Peptide-1 (GLP-1) receptor agonist, is used as a treatment for Type 2 diabetes mellitus and obesity because it improves glycemia and decreases food intake. Here, we tested whether chronic activation of the GLP-1 receptor system with liraglutide would induce decreases in intake accompanied by changes in proportional food or macronutrient intake similar to those seen following RYGB in rats when a variety of palatable food options are available. A "cafeteria diet" was used that included: laboratory rodent chow, refried beans (low-fat/low-sugar), low-fat yogurt (low-fat/high-sugar), peanut butter (high-fat/low-sugar) and sugar-fat whip (high-fat/high-sugar). Liraglutide (1mg/kg daily, sc, n=6) induced significant reductions in body weight and total caloric intake compared to saline-injected control rats (n=6). Although access to a cafeteria diet induced increases in caloric intake in both groups relative to chow alone, liraglutide still effectively decreased intake compared with saline-injected rats suggesting that chronic GLP-1 activation competes with the energy density and palatability of available food options in modulating ingestive behavior. Even with the substantial effects on overall intake, liraglutide did not change food choice or relative macronutrient intake when compared to pre-treatment baseline. When drug treatment was discontinued, the liraglutide group increased caloric intake and rapidly gained body weight to match that of the saline group. These results demonstrate that, while liraglutide effectively decreases caloric intake and body weight in rats, it does not cause adjustments in relative macronutrient consumption. Our data also show that drug-induced decreases in intake and body weight are not maintained following termination of treatment.
Show less
Date Issued: 2017-08-01
Identifier: FSU_pmch_28366815, 10.1016/j.physbeh.2017.03.045, PMC5545097, 28366815, 28366815, S0031-9384(16)31043-5
Format: Citation

Title: Upregulation of an inward rectifying K+ channel can rescue slow Ca2+ oscillations in K(ATP) channel deficient pancreatic islets.
Creator: Yildirim, Vehpi, Vadrevu, Suryakiran, Thompson, Benjamin, Satin, Leslie S, Bertram, Richard
Abstract/Description: Plasma insulin oscillations are known to have physiological importance in the regulation of blood glucose. In insulin-secreting β-cells of pancreatic islets, K(ATP) channels play a key role in regulating glucose-dependent insulin secretion. In addition, they convey oscillations in cellular metabolism to the membrane by sensing adenine nucleotides, and are thus instrumental in mediating pulsatile insulin secretion. Blocking K(ATP) channels pharmacologically depolarizes the β-cell plasma...
Show morePlasma insulin oscillations are known to have physiological importance in the regulation of blood glucose. In insulin-secreting β-cells of pancreatic islets, K(ATP) channels play a key role in regulating glucose-dependent insulin secretion. In addition, they convey oscillations in cellular metabolism to the membrane by sensing adenine nucleotides, and are thus instrumental in mediating pulsatile insulin secretion. Blocking K(ATP) channels pharmacologically depolarizes the β-cell plasma membrane and terminates islet oscillations. Surprisingly, when K(ATP) channels are genetically knocked out, oscillations in islet activity persist, and relatively normal blood glucose levels are maintained. Compensation must therefore occur to overcome the loss of K(ATP) channels in K(ATP) knockout mice. In a companion study, we demonstrated a substantial increase in Kir2.1 protein occurs in β-cells lacking K(ATP) because of SUR1 deletion. In this report, we demonstrate that β-cells of SUR1 null islets have an upregulated inward rectifying K+ current that helps to compensate for the loss of K(ATP) channels. This current is likely due to the increased expression of Kir2.1 channels. We used mathematical modeling to determine whether an ionic current having the biophysical characteristics of Kir2.1 is capable of rescuing oscillations that are similar in period to those of wild-type islets. By experimentally testing a key model prediction we suggest that Kir2.1 current upregulation is a likely mechanism for rescuing the oscillations seen in islets from mice deficient in K(ATP) channels.
Show less
Date Issued: 2017-07-27
Identifier: FSU_pmch_28749940, 10.1371/journal.pcbi.1005686, PMC5549769, 28749940, 28749940, PCOMPBIOL-D-17-00183
Format: Citation

Title: Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats.
Creator: Strong, C E, Schoepfer, K J, Dossat, A M, Saland, S K, Wright, K N, Kabbaj, M
Abstract/Description: Clinical evidence suggests superior antidepressant response over time with a repeated, intermittent ketamine treatment regimen as compared to a single infusion. However, the club drug ketamine is commonly abused. Therefore, the abuse potential of repeated ketamine injections at low doses needs to be investigated. In this study, we investigated the abuse potential of repeated exposure to either 0, 2.5, or 5 mg/kg ketamine administered once weekly for seven weeks. Locomotor activity and...
Show moreClinical evidence suggests superior antidepressant response over time with a repeated, intermittent ketamine treatment regimen as compared to a single infusion. However, the club drug ketamine is commonly abused. Therefore, the abuse potential of repeated ketamine injections at low doses needs to be investigated. In this study, we investigated the abuse potential of repeated exposure to either 0, 2.5, or 5 mg/kg ketamine administered once weekly for seven weeks. Locomotor activity and conditioned place preference (CPP) were assayed to evaluate behavioral sensitization to the locomotor activating effects of ketamine and its rewarding properties, respectively. Our results show that while neither males nor females developed CPP, males treated with 5 mg/kg and females treated with either 2.5 or 5 mg/kg ketamine behaviorally sensitized. Furthermore, dendritic spine density was increased in the NAc of both males and females administered 5 mg/kg ketamine, an effect specific to the NAc shell (NAcSh) in males but to both the NAc core (NAcC) and NAcSh in females. Additionally, males administered 5 mg/kg ketamine displayed increased protein expression of ΔfosB, calcium calmodulin kinase II alpha (CaMKIIα), and brain-derived neurotrophic factor (BDNF), an effect not observed in females administered either dose of ketamine. However, males and females administered 5 mg/kg ketamine displayed increased protein expression of AMPA receptors (GluA1). Taken together, low-dose ketamine, when administered intermittently, induces behavioral sensitization at a lower dose in females than males, accompanied by an increase in spine density in the NAc and protein expression changes in pathways commonly implicated in addiction.
Show less
Date Issued: 2017-07-15
Identifier: FSU_pmch_28479397, 10.1016/j.neuropharm.2017.05.003, PMC5520991, 28479397, 28479397, S0028-3908(17)30199-5
Format: Citation

Title: Nutrient Sensing: Another Chemosensitivity Of The Olfactory System.
Creator: Julliard, A.-Karyn, Al Koborssy, Dolly, Fadool, Debra A., Palouzier-Paulignan, Brigitte
Abstract/Description: Olfaction is a major sensory modality involved in real time perception of the chemical composition of the external environment. Olfaction favors anticipation and rapid adaptation of behavioral responses necessary for animal survival. Furthermore, recent studies have demonstrated that there is a direct action of metabolic peptides on the olfactory network. Orexigenic peptides such as ghrelin and orexin increase olfactory sensitivity, which in turn, is decreased by anorexigenic hormones such as...
Show moreOlfaction is a major sensory modality involved in real time perception of the chemical composition of the external environment. Olfaction favors anticipation and rapid adaptation of behavioral responses necessary for animal survival. Furthermore, recent studies have demonstrated that there is a direct action of metabolic peptides on the olfactory network. Orexigenic peptides such as ghrelin and orexin increase olfactory sensitivity, which in turn, is decreased by anorexigenic hormones such as insulin and leptin. In addition to peptides, nutrients can play a key role on neuronal activity. Very little is known about nutrient sensing in olfactory areas. Nutrients, such as carbohydrates, amino acids, and lipids, could play a key role in modulating olfactory sensitivity to adjust feeding behavior according to metabolic need. Here we summarize recent findings on nutrient-sensing neurons in olfactory areas and delineate the limits of our knowledge on this topic. The present review opens new lines of investigations on the relationship between olfaction and food intake, which could contribute to determining the etiology of metabolic disorders.
Show less
Date Issued: 2017-07-12
Identifier: FSU_libsubv1_wos_000405365400001, 10.3389/fphys.2017.00468
Format: Citation

Title: Upregulation Of An Inward Rectifying K+ Channel Can Rescue Slow Ca2+ Oscillations In K (atp) Channel Deficient Pancreatic Islets.
Creator: Yildirim, Vehpi, Vadrevu, Suryakiran, Thompson, Benjamin, Satin, Leslie S., Bertram, Richard
Abstract/Description: Plasma insulin oscillations are known to have physiological importance in the regulation of blood glucose. In insulin-secreting beta-cells of pancreatic islets, K(ATP) channels play a key role in regulating glucose-dependent insulin secretion. In addition, they convey oscillations in cellular metabolism to the membrane by sensing adenine nucleotides, and are thus instrumental in mediating pulsatile insulin secretion. Blocking K(ATP) channels pharmacologically depolarizes the beta-cell plasma...
Show morePlasma insulin oscillations are known to have physiological importance in the regulation of blood glucose. In insulin-secreting beta-cells of pancreatic islets, K(ATP) channels play a key role in regulating glucose-dependent insulin secretion. In addition, they convey oscillations in cellular metabolism to the membrane by sensing adenine nucleotides, and are thus instrumental in mediating pulsatile insulin secretion. Blocking K(ATP) channels pharmacologically depolarizes the beta-cell plasma membrane and terminates islet oscillations. Surprisingly, when K(ATP) channels are genetically knocked out, oscillations in islet activity persist, and relatively normal blood glucose levels are maintained. Compensation must therefore occur to overcome the loss of K(ATP) channels in K(ATP) knockout mice. In a companion study, we demonstrated a substantial increase in Kir2.1 protein occurs in beta-cells lacking K(ATP) because of SUR1 deletion. In this report, we demonstrate that beta-cells of SUR1 null islets have an upregulated inward rectifying K+ current that helps to compensate for the loss of K (ATP) channels. This current is likely due to the increased expression of Kir2.1 channels. We used mathematical modeling to determine whether an ionic current having the biophysical characteristics of Kir2.1 is capable of rescuing oscillations that are similar in period to those of wild-type islets. By experimentally testing a key model prediction we suggest that Kir2.1 current upregulation is a likely mechanism for rescuing the oscillations seen in islets from mice deficient in K(ATP) channels.
Show less
Date Issued: 2017-07
Identifier: FSU_libsubv1_wos_000406619800052, 10.1371/journal.pcbi.1005686
Format: Citation

Title: An Examination of the Role of L-Glutamate and Inosine 5'-Monophosphate in Hedonic Taste-Guided Behavior by Mice Lacking the T1R1 + T1R3 Receptor.
Creator: Blonde, Ginger D, Spector, Alan C
Abstract/Description: The heterodimeric T1R1 + T1R3 receptor is considered critical for normal signaling of L-glutamate and 5'-ribonucleotides in the oral cavity. However, some taste-guided responsiveness remains in mice lacking one subunit of the receptor, suggesting that other receptors are sufficient to support some behaviors. Here, mice lacking both receptor subunits (KO) and wild-type (WT, both n = 13) mice were tested in a battery of behavioral tests. Mice were trained and tested in gustometers with a...
Show moreThe heterodimeric T1R1 + T1R3 receptor is considered critical for normal signaling of L-glutamate and 5'-ribonucleotides in the oral cavity. However, some taste-guided responsiveness remains in mice lacking one subunit of the receptor, suggesting that other receptors are sufficient to support some behaviors. Here, mice lacking both receptor subunits (KO) and wild-type (WT, both n = 13) mice were tested in a battery of behavioral tests. Mice were trained and tested in gustometers with a concentration series of Maltrin-580, a maltodextrin, in a brief-access test (10-s trials) as a positive control. Similar tests followed with monosodium glutamate (MSG) with and without the ribonucleotide inosine 5'-monophosphate (IMP), but always in the presence of the epithelial sodium channel blocker amiloride (A). Brief-access tests were repeated following short-term (30-min) and long-term (48-h) exposures to MSG + A + IMP and were also conducted with sodium gluconate replacing MSG. Finally, progressive ratio tests were conducted with Maltrin-580 or MSG + A + IMP, to assess appetitive behavior while minimizing satiation. Overall, MSG generated little concentration-dependent responding in either food-restricted WT or KO mice, even in combination with IMP. However, KO mice licked less to the amino acid stimuli, a measure of consummatory behavior in the brief-access tests. In contrast, both groups initiated a similar number of trials and had a similar breakpoint in the progressive ratio task, both measures of appetitive (approach) behavior. Collectively, these results suggest that while the T1R1 + T1R3 receptor is necessary for consummatory responding to MSG (+IMP), other receptors are sufficient to maintain appetitive responding to this "umami" stimulus complex in food-restricted mice.
Show less
Date Issued: 2017-06-01
Identifier: FSU_pmch_28334294, 10.1093/chemse/bjx015, PMC6075476, 28334294, 28334294, 3073965
Format: Citation

Title: Neuromodulation in Chemosensory Pathways.
Creator: McIntyre, Jeremy C, Thiebaud, Nicolas, McGann, John P, Komiyama, Takaki, Rothermel, Markus
Abstract/Description: Interactions with the environment depend not only on sensory perception of external stimuli but also on processes of neuromodulation regulated by the internal state of an organism. These processes allow regulation of stimulus detection to match the demands of an organism influenced by its general brain state (satiety, wakefulness/sleep state, attentiveness, arousal, learning etc.). The sense of smell is initiated by sensory neurons located in the nasal cavity that recognize environmental...
Show moreInteractions with the environment depend not only on sensory perception of external stimuli but also on processes of neuromodulation regulated by the internal state of an organism. These processes allow regulation of stimulus detection to match the demands of an organism influenced by its general brain state (satiety, wakefulness/sleep state, attentiveness, arousal, learning etc.). The sense of smell is initiated by sensory neurons located in the nasal cavity that recognize environmental odorants and project axons into the olfactory bulb (OB), where they form synapses with several types of neurons. Modulations of early synaptic circuits are particularly important since these can affect all subsequent processing steps. While the precise mechanisms have not been fully elucidated, work from many labs has demonstrated that the activity of neurons in the OB and cortex can be modulated by different factors inducing specific changes to olfactory information processing. The symposium "Neuromodulation in Chemosensory Pathways" at the International Symposium on Olfaction and Taste (ISOT 2016) highlighted some of the most recent advances in state-dependent network modulations of the mouse olfactory system including modulation mediated by specific neurotransmitters and neuroendocrine molecules, involving pharmacological, electrophysiological, learning, and behavioral approaches.
Show less
Date Issued: 2017-06-01
Identifier: FSU_pmch_28379355, 10.1093/chemse/bjx014, PMC5863563, 28379355, 28379355, 3100451
Format: Citation

Title: Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice.
Creator: Bell, Genevieve A, Fadool, Debra Ann
Abstract/Description: Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the...
Show moreIntranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5μg/μl of insulin twice daily for 30 and 60days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice did not perform differently than controls, regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3 fold increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors - as reported to elicit a modulatory effect with acute administration. This leads to two alternative interpretations regarding long-term insulin IND in mice: 1) It causes an initial stage of insulin resistance to dampen the behaviors that would normally be modulated under acute insulin IND, but ability to clear a glucose challenge is still retained, or 2) There is a lack of behavioral modulation at high concentration of insulin attributed to the twice daily intervals of hyperinsulinemia caused by insulin IND administration without any insulin resistance, per se.
Show less
Date Issued: 2017-05-15
Identifier: FSU_pmch_28259806, 10.1016/j.physbeh.2017.02.044, PMC5639911, 28259806, 28259806, S0031-9384(16)30820-4
Format: Citation

Title: Alteration Of Neuronal Excitability And Short-term Synaptic Plasticity In The Prefrontal Cortex Of A Mouse Model Of Mental Illness.
Creator: Crabtree, Gregg W., Sun, Ziyi, Kvajo, Mirna, Broek, Jantine A. C., Fenelon, Karine, McKellar, Heather, Xiao, Lan, Xu, Bin, Bahn, Sabine, O'Donnell, James M., Gogos, Joseph A.
Abstract/Description: Using a genetic mouse model that faithfully recapitulates a DISC1 genetic alteration strongly associated with schizophrenia and other psychiatric disorders, we examined the impact of this mutation within the prefrontal cortex. Although cortical layering, cytoarchitecture, and proteome were found to be largely unaffected, electrophysiological examination of the mPFC revealed both neuronal hyperexcitability and alterations in short-term synaptic plasticity consistent with enhanced...
Show moreUsing a genetic mouse model that faithfully recapitulates a DISC1 genetic alteration strongly associated with schizophrenia and other psychiatric disorders, we examined the impact of this mutation within the prefrontal cortex. Although cortical layering, cytoarchitecture, and proteome were found to be largely unaffected, electrophysiological examination of the mPFC revealed both neuronal hyperexcitability and alterations in short-term synaptic plasticity consistent with enhanced neurotransmitter release. Increased excitability of layer II/III pyramidal neurons was accompanied by consistent reductions in voltage-activated potassium currents near the action potential threshold as well as by enhanced recruitment of inputs arising from superficial layers to layer V. We further observed reductions in both the paired-pulse ratios and the enhanced short-term depression of layer V synapses arising from superficial layers consistent with enhanced neurotransmitter release at these synapses. Recordings from layer II/III pyramidal neurons revealed action potential widening that could account for enhanced neurotransmitter release. Significantly, we found that reduced functional expression of the voltagedependent potassium channel subunit K(v)1.1 substantially contributes to both the excitability and short-term plasticity alterations that we observed. The underlying dysregulation of K(v)1.1 expression was attributable to cAMP elevations in the PFC secondary to reduced phosphodiesterase 4 activity present in Disc1 deficiency and was rescued by pharmacological blockade of adenylate cyclase. Our results demonstrate a potentially devastating impact of Disc1 deficiency on neural circuit function, partly due to Kv1.1 dysregulation that leads to a dual dysfunction consisting of enhanced neuronal excitability and altered short-term synaptic plasticity.
Show less
Date Issued: 2017-04-12
Identifier: FSU_libsubv1_wos_000399440400015, 10.1523/JNEUROSCI.4345-15.2017
Format: Citation

Title: Alteration of Neuronal Excitability and Short-Term Synaptic Plasticity in the Prefrontal Cortex of a Mouse Model of Mental Illness.
Creator: Crabtree, Gregg W, Sun, Ziyi, Kvajo, Mirna, Broek, Jantine A C, Fénelon, Karine, McKellar, Heather, Xiao, Lan, Xu, Bin, Bahn, Sabine, O'Donnell, James M, Gogos, Joseph A
Abstract/Description: Using a genetic mouse model that faithfully recapitulates a genetic alteration strongly associated with schizophrenia and other psychiatric disorders, we examined the impact of this mutation within the prefrontal cortex. Although cortical layering, cytoarchitecture, and proteome were found to be largely unaffected, electrophysiological examination of the mPFC revealed both neuronal hyperexcitability and alterations in short-term synaptic plasticity consistent with enhanced neurotransmitter...
Show moreUsing a genetic mouse model that faithfully recapitulates a genetic alteration strongly associated with schizophrenia and other psychiatric disorders, we examined the impact of this mutation within the prefrontal cortex. Although cortical layering, cytoarchitecture, and proteome were found to be largely unaffected, electrophysiological examination of the mPFC revealed both neuronal hyperexcitability and alterations in short-term synaptic plasticity consistent with enhanced neurotransmitter release. Increased excitability of layer II/III pyramidal neurons was accompanied by consistent reductions in voltage-activated potassium currents near the action potential threshold as well as by enhanced recruitment of inputs arising from superficial layers to layer V. We further observed reductions in both the paired-pulse ratios and the enhanced short-term depression of layer V synapses arising from superficial layers consistent with enhanced neurotransmitter release at these synapses. Recordings from layer II/III pyramidal neurons revealed action potential widening that could account for enhanced neurotransmitter release. Significantly, we found that reduced functional expression of the voltage-dependent potassium channel subunit K1.1 substantially contributes to both the excitability and short-term plasticity alterations that we observed. The underlying dysregulation of K1.1 expression was attributable to cAMP elevations in the PFC secondary to reduced phosphodiesterase 4 activity present in Disc1 deficiency and was rescued by pharmacological blockade of adenylate cyclase. Our results demonstrate a potentially devastating impact of Disc1 deficiency on neural circuit function, partly due to K1.1 dysregulation that leads to a dual dysfunction consisting of enhanced neuronal excitability and altered short-term synaptic plasticity. Schizophrenia is a profoundly disabling psychiatric illness with a devastating impact not only upon the afflicted but also upon their families and the broader society. Although the underlying causes of schizophrenia remain poorly understood, a growing body of studies has identified and strongly implicated various specific risk genes in schizophrenia pathogenesis. Here, using a genetic mouse model, we explored the impact of one of the most highly penetrant schizophrenia risk genes, , upon the medial prefrontal cortex, the region believed to be most prominently dysfunctional in schizophrenia. We found substantial derangements in both neuronal excitability and short-term synaptic plasticity-parameters that critically govern neural circuit information processing-suggesting that similar changes may critically, and more broadly, underlie the neural computational dysfunction prototypical of schizophrenia.
Show less
Date Issued: 2017-04-12
Identifier: FSU_pmch_28283561, 10.1523/JNEUROSCI.4345-15.2017, PMC5391686, 28283561, 28283561, JNEUROSCI.4345-15.2017
Format: Citation

Title: Dopamine: A Modulator Of Circadian Rhythms In The Central Nervous System.
Creator: Korshunov, Kirill S., Blakemore, Laura J., Trombley, Paul Q.
Abstract/Description: Circadian rhythms are daily rhythms that regulate many biological processes - from gene transcription to behavior - and a disruption of these rhythms can lead to a myriad of health risks. Circadian rhythms are entrained by light, and their 24-h oscillation is maintained by a core molecular feedback loop composed of canonical circadian ("clock") genes and proteins. Different modulators help to maintain the proper rhythmicity of these genes and proteins, and one emerging modulator is dopamine....
Show moreCircadian rhythms are daily rhythms that regulate many biological processes - from gene transcription to behavior - and a disruption of these rhythms can lead to a myriad of health risks. Circadian rhythms are entrained by light, and their 24-h oscillation is maintained by a core molecular feedback loop composed of canonical circadian ("clock") genes and proteins. Different modulators help to maintain the proper rhythmicity of these genes and proteins, and one emerging modulator is dopamine. Dopamine has been shown to have circadian-like activities in the retina, olfactory bulb, striatum, midbrain, and hypothalamus, where it regulates, and is regulated by, clock genes in some of these areas. Thus, it is likely that dopamine is essential to mechanisms that maintain proper rhythmicity of these five brain areas. This review discusses studies that showcase different dopaminergic mechanisms that may be involved with the regulation of these brain areas' circadian rhythms. Mechanisms include how dopamine and dopamine receptor activity directly and indirectly influence clock genes and proteins, how dopamine's interactions with gap junctions influence daily neuronal excitability, and how dopamine's release and effects are gated by low- and high-pass filters. Because the dopamine neurons described in this review also release the inhibitory neurotransmitter GABA which influences clock protein expression in the retina, we discuss articles that explore how GABA may contribute to the actions of dopamine neurons on circadian rhythms. Finally, to understand how the loss of function of dopamine neurons could influence circadian rhythms, we review studies linking the neurodegenerative disease Parkinson's Disease to disruptions of circadian rhythms in these five brain areas. The purpose of this review is to summarize growing evidence that dopamine is involved in regulating circadian rhythms, either directly or indirectly, in the brain areas discussed here. An appreciation of the growing evidence of dopamine's influence on circadian rhythms may lead to new treatments including pharmacological agents directed at alleviating the various symptoms of circadian rhythm disruption.
Show less
Date Issued: 2017-04-03
Identifier: FSU_libsubv1_wos_000398490600001, 10.3389/fncel.2017.00091
Format: Citation

Title: Integrative analysis of sex differences in the rapid antidepressant effects of ketamine in preclinical models for individualized clinical outcomes.
Creator: Saland, Samantha K, Duclot, Florian, Kabbaj, Mohamed
Abstract/Description: In major depressive disorder, women exhibit higher lifetime prevalence and different antidepressant response rates than men, which illustrates the importance of examining individual differences in the pathophysiology of depression and therapeutic response. In recent years, the consideration of sex in related preclinical research has thus gained interest-particularly in light of novel evidence for rapid-acting antidepressants. Notably, the literature recently revealed a higher sensitivity of...
Show moreIn major depressive disorder, women exhibit higher lifetime prevalence and different antidepressant response rates than men, which illustrates the importance of examining individual differences in the pathophysiology of depression and therapeutic response. In recent years, the consideration of sex in related preclinical research has thus gained interest-particularly in light of novel evidence for rapid-acting antidepressants. Notably, the literature recently revealed a higher sensitivity of females to the antidepressant effects of the N-methyl-D-aspartate receptor antagonist ketamine, in both baseline and preclinical conditions. Combined with its fast-acting and relatively sustained properties, this evidence highlights ketamine as a particularly interesting therapeutic alternative for this sensitive population, and supports the value in considering sex as a critical factor for improved individualized therapeutic strategies.
Show less
Date Issued: 2017-04-01
Identifier: FSU_pmch_28584860, 10.1016/j.cobeha.2016.11.002, PMC5456295, 28584860, 28584860
Format: Citation

Title: Oxytocin receptor binding sites in the periphery of the neonatal mouse.
Creator: Greenwood, Maria A, Hammock, Elizabeth A D
Abstract/Description: Oxytocin (OXT) is a pleiotropic regulator of physiology and behavior. An emerging body of evidence demonstrates a role for OXT in the transition to postnatal life of the infant. To identify potential sites of OXT action via the OXT receptor (OXTR) in the newborn mouse, we performed receptor autoradiography on 20 μm sagittal sections of whole postnatal day 0 male and female mice on a C57BL/6J background using the 125iodinated ornithine vasotocin analog ([125I]-OVTA) radioligand. A competitive...
Show moreOxytocin (OXT) is a pleiotropic regulator of physiology and behavior. An emerging body of evidence demonstrates a role for OXT in the transition to postnatal life of the infant. To identify potential sites of OXT action via the OXT receptor (OXTR) in the newborn mouse, we performed receptor autoradiography on 20 μm sagittal sections of whole postnatal day 0 male and female mice on a C57BL/6J background using the 125iodinated ornithine vasotocin analog ([125I]-OVTA) radioligand. A competitive binding assay on both wild-type (WT) and OXTR knockout (OXTR KO) tissue was used to assess the selectivity of [125I]-OVTA for neonatal OXTR. Radioactive ligand (0.05 nM [125I]-OVTA) was competed against concentrations of 0 nM, 10 nM, and 1000 nM excess unlabeled OXT. Autoradiographs demonstrated the high selectivity of the radioligand for infant peripheral OXTR. Specific ligand binding activity for OXTR was observed in the oronasal cavity, the eye, whisker pads, adrenal gland, and anogenital region in the neonatal OXTR WT mouse, but was absent in neonatal OXTR KO. Nonspecific binding was observed in areas with a high lipid content such as the scapular brown adipose tissue and the liver: in these regions, binding was present in both OXTR WT and KO mice, and could not be competed away with OXT in either WT or KO mice. Collectively, these data confirm novel OXT targets in the periphery of the neonate. These peripheral OXTR sites, coupled with the immaturity of the neonate's own OXT system, suggest a role for exogenous OXT in modulating peripheral physiology and development.
Show less
Date Issued: 2017-02-24
Identifier: FSU_pmch_28235051, 10.1371/journal.pone.0172904, PMC5325587, 28235051, 28235051, PONE-D-16-44673
Format: Citation

Title: Paternal deprivation affects social behaviors and neurochemical systems in the offspring of socially monogamous prairie voles.
Creator: Tabbaa, Manal, Lei, Kelly, Liu, Yan, Wang, Zuoxin
Abstract/Description: Early life experiences, particularly the experience with parents, are crucial to phenotypic outcomes in both humans and animals. Although the effects of maternal deprivation on offspring well-being have been studied, paternal deprivation (PD) has received little attention despite documented associations between father absence and children health problems in humans. In the present study, we utilized the socially monogamous prairie vole (Microtus ochrogaster), which displays male-female pair...
Show moreEarly life experiences, particularly the experience with parents, are crucial to phenotypic outcomes in both humans and animals. Although the effects of maternal deprivation on offspring well-being have been studied, paternal deprivation (PD) has received little attention despite documented associations between father absence and children health problems in humans. In the present study, we utilized the socially monogamous prairie vole (Microtus ochrogaster), which displays male-female pair bonding and bi-parental care, to examine the effects of PD on adult behaviors and neurochemical expression in the hippocampus. Male and female subjects were randomly assigned into one of two experimental groups that grew up with both the mother and father (MF) or with the mother-only (MO, to generate PD experience). Our data show that MO subjects received less parental licking/grooming and carrying and were left alone in the nest more frequently than MF subjects. At adulthood (∼75days of age), MO subjects displayed increased social affiliation (SOA) toward a conspecific compared to MF subjects, but the two groups did not differ in social recognition (SOR) and anxiety-like behavior. Interestingly, MO subjects showed consistent increases in both gene and protein expression of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) as well as the levels of total histone 3 and histone 3 acetylation in the hippocampus compared to MF subjects. Further, PD experience increased glucocorticoid receptor beta (GRβ) protein expression in the hippocampus of females as well as increased corticotrophin receptor 2 (CRHR2) protein expression in the hippocampus of males, but decreased CRHR2 mRNA in both sexes. Together, our data suggest that PD has a long-lasting, behavior-specific effect on SOA and alters hippocampal neurochemical systems in the vole brain. The functional role of such altered neurochemical systems in social behaviors and the potential involvement of epigenetic events should be further studied.
Show less
Date Issued: 2017-02-20
Identifier: FSU_pmch_27998780, 10.1016/j.neuroscience.2016.12.011, PMC5266501, 27998780, 27998780, S0306-4522(16)30701-1
Format: Citation

Title: Neurochemical Mediation of Affiliation and Aggression Associated With Pair-Bonding.
Creator: Gobrogge, Kyle L, Jia, Xixi, Liu, Yan, Wang, Zuoxin
Abstract/Description: The neuropeptides vasopressin and corticotropin-releasing factor facilitate, while serotonin inhibits, aggression. How the brain is wired to coordinate interactions between these functionally opposed neurotransmitters to control behavioral states is poorly understood. Pair-bonded male prairie voles (Microtus ochrogaster) were infused with a retrograde tracer, Fluoro-Gold, and tested for affiliation and aggression toward a female partner or novel female subject. Subsequent immunocytochemical...
Show moreThe neuropeptides vasopressin and corticotropin-releasing factor facilitate, while serotonin inhibits, aggression. How the brain is wired to coordinate interactions between these functionally opposed neurotransmitters to control behavioral states is poorly understood. Pair-bonded male prairie voles (Microtus ochrogaster) were infused with a retrograde tracer, Fluoro-Gold, and tested for affiliation and aggression toward a female partner or novel female subject. Subsequent immunocytochemical experiments examined neuronal activation using Fos and neurochemical/neuroreceptor profiles on brain areas involved in these social behaviors. Finally, a series of behavioral pharmacologic and real-time in vivo brain microdialysis experiments were performed on male prairie voles displaying affiliation or aggression. We localized a subpopulation of excitatory vasopressin neurons in the anterior hypothalamus that may gate corticotropin-releasing factor output from the amygdala to the anterior hypothalamus and then the lateral septum to modulate aggression associated with mate guarding. Conversely, we identified a subset of inhibitory serotonergic projection neurons in the dorsal raphe that project to the anterior hypothalamus and may mediate the spatiotemporal release of neuropeptides and their interactions in modulating aggression and affiliation. Together, this study establishes the medial extended amygdala as a major neural substrate regulating the switch between positive and negative affective states, wherein several neurochemicals converge and interact to coordinate divergent social behaviors.
Show less
Date Issued: 2017-02-01
Identifier: FSU_pmch_27129413, 10.1016/j.biopsych.2016.02.013, PMC4992658, 27129413, 27129413, S0006-3223(16)00100-1
Format: Citation

Title: Reinforcing properties of an intermittent, low dose of ketamine in rats: effects of sex and cycle..
Creator: Wright, Katherine N, Strong, Caroline E, Addonizio, Marjorie N, Brownstein, Naomi C, Kabbaj, Mohamed
Abstract/Description: Repeated intermittent exposure to ketamine has rapid and long-lasting antidepressant effects, but the abuse potential has only been assessed at high doses. Furthermore, while females are more susceptible to depression and more sensitive to ketamine's antidepressant-like effects, the abuse potential for ketamine in females is unknown. The objectives of this study are to determine the reinforcing properties of low-dose intermittent ketamine in adult rats of both sexes and determine whether...
Show moreRepeated intermittent exposure to ketamine has rapid and long-lasting antidepressant effects, but the abuse potential has only been assessed at high doses. Furthermore, while females are more susceptible to depression and more sensitive to ketamine's antidepressant-like effects, the abuse potential for ketamine in females is unknown. The objectives of this study are to determine the reinforcing properties of low-dose intermittent ketamine in adult rats of both sexes and determine whether cycling gonadal hormones influence females' response to ketamine. In male rats, we also aimed to determine whether reinstatement to intermittent ketamine is comparable to intermittent cocaine. Male rats intravenously self-administered cocaine (0.75 mg/kg/infusion) or ketamine (0.1 mg/kg/infusion) once every fourth day, while intact cycling female rats self-administered ketamine only during preidentified stages of their 4-day estrus cycle, when gonadal hormones are either high (proestrus) or low (diestrus). After acquiring self-administration, rats underwent daily extinction training followed by cue-primed and drug-primed reinstatement to assess drug-seeking behavior. Diestrus-trained females fail to maintain ketamine self-administration and did not display reinstatement to ketamine-paired cues. Males and proestrus-trained females reinstated to ketamine-paired cues. Ketamine-primed reinstatement was dependent on simultaneous cue presentation. Male rats reinstated to cocaine priming independent of cue presentation. These findings indicate that females's responsivity to this dose of ketamine depends on stage of cycle, as only proestrus-trained females and males respond to ketamine's reinforcing effects under this treatment paradigm.
Show less
Date Issued: 2017-02-01
Identifier: FSU_pmch_27837330, 10.1007/s00213-016-4470-z, PMC5384643, 27837330, 27837330, 10.1007/s00213-016-4470-z
Format: Citation

Title: Margatoxin-bound quantum dots as a novel inhibitor of the voltage-gated ion channel Kv1.3.
Creator: Schwartz, Austin B, Kapur, Anshika, Wang, Wentao, Huang, Zhenbo, Fardone, Erminia, Palui, Goutam, Mattoussi, Hedi, Fadool, Debra Ann
Abstract/Description: Venom-derived ion channel inhibitors have strong channel selectivity, potency, and stability; however, tracking delivery to their target can be challenging. Herein, we utilized luminescent quantum dots (QDs) conjugated to margatoxin (MgTx) as a traceable vehicle to target a voltage-dependent potassium channel, Kv1.3, which has a select distribution and well-characterized role in immunity, glucose metabolism, and sensory ability. We screened both unconjugated (MgTx) and conjugated MgTx (QD...
Show moreVenom-derived ion channel inhibitors have strong channel selectivity, potency, and stability; however, tracking delivery to their target can be challenging. Herein, we utilized luminescent quantum dots (QDs) conjugated to margatoxin (MgTx) as a traceable vehicle to target a voltage-dependent potassium channel, Kv1.3, which has a select distribution and well-characterized role in immunity, glucose metabolism, and sensory ability. We screened both unconjugated (MgTx) and conjugated MgTx (QD-MgTx) for their ability to inhibit Shaker channels Kv1.1 to Kv1.7 using patch-clamp electrophysiology in HEK293 cells. Our data indicate that MgTx inhibits 79% of the outward current in Kv1.3-transfected cells and that the QD-MgTx conjugate is able to achieve a similar level of block, albeit a slightly reduced efficacy (66%) and at a slower time course (50% block by 10.9 ± 1.1 min, MgTx; vs. 15.3 ± 1.2 min, QD-MgTx). Like the unbound peptide, the QD-MgTx conjugate inhibits both Kv1.3 and Kv1.2 at a 1 nM concentration, whereas it does not inhibit other screened Shaker channels. We tested the ability of QD-MgTx to inhibit native Kv1.3 expressed in the mouse olfactory bulb (OB). In brain slices of the OB, the conjugate acted similarly to MgTx to inhibit Kv1.3, causing an increased action potential firing frequency attributed to decreased intraburst duration rather than interspike interval. Our data demonstrate a retention of known biophysical properties associated with block of the vestibule of Kv1.3 by QD-MgTx conjugate compared to that of MgTx, inferring QDs could provide a useful tool to deliver ion channel inhibitors to targeted tissues in vivo.
Show less
Date Issued: 2017-02-01
Identifier: FSU_pmch_27861889, 10.1111/jnc.13891, PMC5250575, 27861889, 27861889
Format: Citation

Title: Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats.
Creator: Dossat, Amanda M, Jourdi, Hussam, Wright, Katherine N, Strong, Caroline E, Sarkar, Ambalika, Kabbaj, Mohamed
Abstract/Description: In humans, some males experience reductions in testosterone levels, as a natural consequence of aging or in the clinical condition termed hypogonadism, which are associated with impaired cognitive performance and mood disorder(s). Some of these behavioral deficits can be reversed by testosterone treatment. Our previous work in rats reported that sex differences in the expression of the transcription factor Zif268, a downstream target of testosterone, within the medial prefrontal cortex (mPFC)...
Show moreIn humans, some males experience reductions in testosterone levels, as a natural consequence of aging or in the clinical condition termed hypogonadism, which are associated with impaired cognitive performance and mood disorder(s). Some of these behavioral deficits can be reversed by testosterone treatment. Our previous work in rats reported that sex differences in the expression of the transcription factor Zif268, a downstream target of testosterone, within the medial prefrontal cortex (mPFC) mediates sex differences in social interaction. In the present study, we aimed to examine the effects of gonadectomy (GNX) in male rats on mPFC Zif268 expression, mood and cognitive behaviors. We also examined whether reinstitution of Zif268 in GNX rats will correct some of the behavioral deficits observed following GNX. Our results show that GNX induced a downregulation of Zif268 protein in the mPFC, which was concomitant with impaired memory in the y-maze and spontaneous object recognition test, reduced social interaction time, and depression-like behaviors in the forced swim test. Reinstitution of mPFC Zif268, using a novel adeno-associated-viral (AAV) construct, abrogated GNX-induced working memory and long-term memory impairments, and reductions in social interaction time, but not GNX-induced depression-like behaviors. These findings suggest that mPFC Zif268 exerts beneficial effects on memory and social interaction, and could be a potential target for novel treatments for behavioral impairments observed in hypogonadal and aged men with declining levels of gonadal hormones.
Show less
Date Issued: 2017-01-06
Identifier: FSU_pmch_27816701, 10.1016/j.neuroscience.2016.10.062, PMC5154846, 27816701, 27816701, S0306-4522(16)30603-0
Format: Citation

Title: Differential role of calpain-dependent protein cleavage in intermediate and long-term operant memory in Aplysia.
Creator: Lyons, Lisa C, Gardner, Jacob S, Lentsch, Cassidy T, Gandour, Catherine E, Krishnan, Harini C, Noakes, Eric J
Abstract/Description: In addition to protein synthesis, protein degradation or protein cleavage may be necessary for intermediate (ITM) and long-term memory (LTM) to remove molecular constraints, facilitate persistent kinase activity and modulate synaptic plasticity. Calpains, a family of conserved calcium dependent cysteine proteases, modulate synaptic function through protein cleavage. We used the marine mollusk Aplysia californica to investigate the in vivo role of calpains during intermediate and long-term...
Show moreIn addition to protein synthesis, protein degradation or protein cleavage may be necessary for intermediate (ITM) and long-term memory (LTM) to remove molecular constraints, facilitate persistent kinase activity and modulate synaptic plasticity. Calpains, a family of conserved calcium dependent cysteine proteases, modulate synaptic function through protein cleavage. We used the marine mollusk Aplysia californica to investigate the in vivo role of calpains during intermediate and long-term operant memory formation using the learning that food is inedible (LFI) paradigm. A single LFI training session, in which the animal associates a specific netted seaweed with the failure to swallow, generates short (30min), intermediate (4-6h) and long-term (24h) memory. Using the calpain inhibitors calpeptin and MDL-28170, we found that ITM requires calpain activity for induction and consolidation similar to the previously reported requirements for persistent protein kinase C activity in intermediate-term LFI memory. The induction of LTM also required calpain activity. In contrast to ITM, calpain activity was not necessary for the molecular consolidation of LTM. Surprisingly, six hours after LFI training we found that calpain activity was necessary for LTM, although this is a time at which neither persistent PKC activity nor protein synthesis is required for the maintenance of long-term LFI memory. These results demonstrate that calpains function in multiple roles in vivo during associative memory formation.
Show less
Date Issued: 2017-01-01
Identifier: FSU_pmch_27913293, 10.1016/j.nlm.2016.11.018, PMC6179366, 27913293, 27913293, S1074-7427(16)30358-6
Format: Citation

Creator: De Nobrega, Aliza K, Lyons, Lisa C
Abstract/Description: Endogenous circadian oscillators orchestrate rhythms at the cellular, physiological, and behavioral levels across species to coordinate activity, for example, sleep/wake cycles, metabolism, and learning and memory, with predictable environmental cycles. The 21st century has seen a dramatic rise in the incidence of circadian and sleep disorders with globalization, technological advances, and the use of personal electronics. The circadian clock modulates alcohol- and drug-induced behaviors with...
Show moreEndogenous circadian oscillators orchestrate rhythms at the cellular, physiological, and behavioral levels across species to coordinate activity, for example, sleep/wake cycles, metabolism, and learning and memory, with predictable environmental cycles. The 21st century has seen a dramatic rise in the incidence of circadian and sleep disorders with globalization, technological advances, and the use of personal electronics. The circadian clock modulates alcohol- and drug-induced behaviors with circadian misalignment contributing to increased substance use and abuse. Invertebrate models, such as , have proven invaluable for the identification of genetic and molecular mechanisms underlying highly conserved processes including the circadian clock, drug tolerance, and reward systems. In this review, we highlight the contributions of as a model system for understanding the bidirectional interactions between the circadian system and the drugs of abuse, alcohol and cocaine, and illustrate the highly conserved nature of these interactions between and mammalian systems. Research in provides mechanistic insights into the corresponding behaviors in higher organisms and can be used as a guide for targeted inquiries in mammals.
Show less
Date Issued: 2017-01-01
Identifier: FSU_pmch_29391952, 10.1155/2017/4723836, PMC5748135, 29391952, 29391952
Format: Citation

Title: Role of proteasome-dependent protein degradation in long-term operant memory in Aplysia.
Creator: Lyons, Lisa C, Gardner, Jacob S, Gandour, Catherine E, Krishnan, Harini C
Abstract/Description: We investigated the in vivo role of protein degradation during intermediate (ITM) and long-term memory (LTM) in Aplysia using an operant learning paradigm. The proteasome inhibitor MG-132 inhibited the induction and molecular consolidation of LTM with no effect on ITM. Remarkably, maintenance of steady-state protein levels through inhibition of protein synthesis using either anisomycin or rapamycin in conjunction with proteasome inhibition permitted the formation of robust 24 h LTM. Our...
Show moreWe investigated the in vivo role of protein degradation during intermediate (ITM) and long-term memory (LTM) in Aplysia using an operant learning paradigm. The proteasome inhibitor MG-132 inhibited the induction and molecular consolidation of LTM with no effect on ITM. Remarkably, maintenance of steady-state protein levels through inhibition of protein synthesis using either anisomycin or rapamycin in conjunction with proteasome inhibition permitted the formation of robust 24 h LTM. Our studies suggest a primary role for proteasomal activity in facilitation of gene transcription for LTM and raise the possibility that synaptic mechanisms are sufficient to sustain 24 h memory.
Show less
Date Issued: 2016-12-15
Identifier: FSU_pmch_27980077, 10.1101/lm.043794.116, PMC5159658, 27980077, 27980077, 24/1/59
Format: Citation

Title: Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis.
Creator: Kettner, Nicole M, Voicu, Horatio, Finegold, Milton J, Coarfa, Cristian, Sreekumar, Arun, Putluri, Nagireddy, Katchy, Chinenye A, Lee, Choogon, Moore, David D, Fu, Loning
Abstract/Description: Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a mechanism very similar to that observed in obese humans. The process initiates with non-alcoholic fatty liver disease (NAFLD) that progresses to steatohepatitis and fibrosis before HCC detection. This pathophysiological pathway is driven by jet-lag-induced genome-wide gene deregulation and global liver metabolic dysfunction, with nuclear receptor-controlled cholesterol/bile acid and xenobiotic...
Show moreChronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a mechanism very similar to that observed in obese humans. The process initiates with non-alcoholic fatty liver disease (NAFLD) that progresses to steatohepatitis and fibrosis before HCC detection. This pathophysiological pathway is driven by jet-lag-induced genome-wide gene deregulation and global liver metabolic dysfunction, with nuclear receptor-controlled cholesterol/bile acid and xenobiotic metabolism among the top deregulated pathways. Ablation of farnesoid X receptor dramatically increases enterohepatic bile acid levels and jet-lag-induced HCC, while loss of constitutive androstane receptor (CAR), a well-known liver tumor promoter that mediates toxic bile acid signaling, inhibits NAFLD-induced hepatocarcinogenesis. Circadian disruption activates CAR by promoting cholestasis, peripheral clock disruption, and sympathetic dysfunction.
Show less
Date Issued: 2016-12-12
Identifier: FSU_pmch_27889186, 10.1016/j.ccell.2016.10.007, PMC5695235, 27889186, 27889186, S1535-6108(16)30494-9
Format: Citation

Title: Neuropeptide Regulation of Social Attachment: The Prairie Vole Model..
Creator: Tabbaa, Manal, Paedae, Brennan, Liu, Yan, Wang, Zuoxin
Abstract/Description: Social attachments are ubiquitous among humans and integral to human health. Although great efforts have been made to elucidate the neural underpinnings regulating social attachments, we still know relatively little about the neuronal and neurochemical regulation of social attachments. As a laboratory animal research model, the socially monogamous prairie vole (Microtus ochrogaster) displays behaviors paralleling human social attachments and thus has provided unique insights into the neural...
Show moreSocial attachments are ubiquitous among humans and integral to human health. Although great efforts have been made to elucidate the neural underpinnings regulating social attachments, we still know relatively little about the neuronal and neurochemical regulation of social attachments. As a laboratory animal research model, the socially monogamous prairie vole (Microtus ochrogaster) displays behaviors paralleling human social attachments and thus has provided unique insights into the neural regulation of social behaviors. Research in prairie voles has particularly highlighted the significance of neuropeptidergic regulation of social behaviors, especially of the roles of oxytocin (OT) and vasopressin (AVP). This article aims to review these findings. We begin by discussing the role of the OT and AVP systems in regulating social behaviors relevant to social attachments, and thereafter restrict our discussion to studies in prairie voles. Specifically, we discuss the role of OT and AVP in adult mate attachments, biparental care, social isolation, and social buffering as informed by studies utilizing the prairie vole model. Not only do these studies offer insight into social attachments in humans, but they also point to dysregulated mechanisms in several mental disorders. We conclude by discussing these implications for human health. © 2017 American Physiological Society. Compr Physiol 7:81-104, 2017.
Show less
Date Issued: 2016-12-06
Identifier: FSU_pmch_28135000, 10.1002/cphy.c150055, PMC5308882, 28135000, 28135000
Format: Citation

Title: Prostaglandin levels, vaginal innervation, and cyst innervation as peripheral contributors to endometriosis-associated vaginal hyperalgesia in rodents.
Creator: McAllister, Stacy L, Giourgas, Barbra K, Faircloth, Elizabeth K, Leishman, Emma, Bradshaw, Heather B, Gross, Eric R
Abstract/Description: Endometriosis is a painful condition characterized by growth of endometrial cysts outside the uterus. Here, we tested the hypothesis that peripheral innervation and prostaglandin levels contribute to endometriosis-associated pain. Female Sprague-Dawley rats (n = 16) were surgically instrumented by transplanting uterine tissue onto mesenteric arteries within the peritoneal cavity to create a model of endometriosis which forms extra-uterine endometrial cysts and vaginal hyperalgesia. Our...
Show moreEndometriosis is a painful condition characterized by growth of endometrial cysts outside the uterus. Here, we tested the hypothesis that peripheral innervation and prostaglandin levels contribute to endometriosis-associated pain. Female Sprague-Dawley rats (n = 16) were surgically instrumented by transplanting uterine tissue onto mesenteric arteries within the peritoneal cavity to create a model of endometriosis which forms extra-uterine endometrial cysts and vaginal hyperalgesia. Our results describe a significant positive correlation between endometriosis-induced vaginal hyperalgesia and cyst innervation density (sensory, r = 0.70, p = 0.003; sympathetic, r = 0.55, p = 0.03), vaginal canal sympathetic innervation density (r = 0.80, p = 0.003), and peritoneal fluid levels of the prostaglandins PGE2 (r = 0.65, p = 0.01) and PGF2α (r = 0.63, p = 0.02). These results support the involvement of cyst innervation and prostaglandins in endometriosis-associated pain. We also describe how sympathetic innervation density of the vaginal canal is an important predictor of vaginal hyperalgesia.
Show less
Date Issued: 2016-12-05
Identifier: FSU_pmch_27524411, 10.1016/j.mce.2016.08.017, PMC5048574, 27524411, 27524411, S0303-7207(16)30311-2
Format: Citation

Title: Acute Sleep Deprivation Blocks Short- and Long-Term Operant Memory in .
Creator: Krishnan, Harini C, Gandour, Catherine E, Ramos, Joshua L, Wrinkle, Mariah C, Sanchez-Pacheco, Joseph J, Lyons, Lisa C
Abstract/Description: Insufficient sleep in individuals appears increasingly common due to the demands of modern work schedules and technology use. Consequently, there is a growing need to understand the interactions between sleep deprivation and memory. The current study determined the effects of acute sleep deprivation on short and long-term associative memory using the marine mollusk , a relatively simple model system well known for studies of learning and memory. were sleep deprived for 9 hours using context...
Show moreInsufficient sleep in individuals appears increasingly common due to the demands of modern work schedules and technology use. Consequently, there is a growing need to understand the interactions between sleep deprivation and memory. The current study determined the effects of acute sleep deprivation on short and long-term associative memory using the marine mollusk , a relatively simple model system well known for studies of learning and memory. were sleep deprived for 9 hours using context changes and tactile stimulation either prior to or after training for the operant learning paradigm, learning that food is inedible (LFI). The effects of sleep deprivation on short-term (STM) and long-term memory (LTM) were assessed. Acute sleep deprivation prior to LFI training impaired the induction of STM and LTM with persistent effects lasting at least 24 h. Sleep deprivation immediately after training blocked the consolidation of LTM. However, sleep deprivation following the period of molecular consolidation did not affect memory recall. Memory impairments were independent of handling-induced stress, as daytime handled control animals demonstrated no memory deficits. Additional training immediately after sleep deprivation failed to rescue the induction of memory, but additional training alleviated the persistent impairment in memory induction when training occurred 24 h following sleep deprivation. Acute sleep deprivation inhibited the induction and consolidation, but not the recall of memory. These behavioral studies establish as an effective model system for studying the interactions between sleep and memory formation.
Show less
Date Issued: 2016-12-01
Identifier: FSU_pmch_27748243, 10.5665/sleep.6320, PMC5103805, 27748243, 27748243, sp-00313-16
Format: Citation

Title: Dual Detection System for Simultaneous Measurement of Intracellular Fluorescent Markers and Cellular Secretion.
Creator: Yi, Lian, Bandak, Basel, Wang, Xue, Bertram, Richard, Roper, Michael G
Abstract/Description: Glucose-stimulated insulin secretion from pancreatic β-cells within islets of Langerhans plays a critical role in maintaining glucose homeostasis. Although this process is essential for maintaining euglycemia, the underlying intracellular mechanisms that control it are still unclear. To allow simultaneous correlation between intracellular signal transduction events and extracellular secretion, an analytical system was developed that integrates fluorescence imaging of intracellular probes with...
Show moreGlucose-stimulated insulin secretion from pancreatic β-cells within islets of Langerhans plays a critical role in maintaining glucose homeostasis. Although this process is essential for maintaining euglycemia, the underlying intracellular mechanisms that control it are still unclear. To allow simultaneous correlation between intracellular signal transduction events and extracellular secretion, an analytical system was developed that integrates fluorescence imaging of intracellular probes with high-speed automated insulin immunoassays. As a demonstration of the system, intracellular [Ca] ([Ca]) was measured by imaging Fura-2 fluorescence simultaneously with insulin secretion from islets exposed to elevated glucose levels. Both [Ca] and insulin were oscillatory during application of 10 mM glucose with temporal and quantitative profiles similar to what has been observed elsewhere. In previous work, sinusoidal glucose levels have been used to test the entrainment of islets while monitoring either [Ca] or insulin levels; using this newly developed system, we show unambiguously that oscillations of both [Ca] and insulin release are entrained to oscillatory glucose levels and that the temporal correlation of these are maintained throughout the experiment. It is expected that the developed analytical system can be expanded to investigate a number of other intracellular messengers in islets or other stimulus-secretion pathways in different cells.
Show less
Date Issued: 2016-11-01
Identifier: FSU_pmch_27712062, 10.1021/acs.analchem.6b02404, PMC5089909, 27712062, 27712062
Format: Citation

Title: Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets.
Creator: McKenna, Joseph P, Dhumpa, Raghuram, Mukhitov, Nikita, Roper, Michael G, Bertram, Richard
Abstract/Description: Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with...
Show morePancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with mathematical modeling that the sinusoidal glucose signal's ability to recover islet oscillations depends on its amplitude and period, and we confirm our predictions by conducting experiments with islets using a microfluidics platform. Our results suggest a mechanism whereby oscillatory blood glucose levels recruit non-oscillating islets to enhance pulsatile insulin output from the pancreas. Our results also provide support for the main hypothesis of the Dual Oscillator Model, that a glycolytic oscillator endogenous to islet β-cells drives pulsatile insulin secretion.
Show less
Date Issued: 2016-10-27
Identifier: FSU_pmch_27788129, 10.1371/journal.pcbi.1005143, PMC5082885, 27788129, 27788129, PCOMPBIOL-D-16-00306
Format: Citation

Title: Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine.
Creator: Duclot, Florian, Perez-Taboada, Iara, Wright, Katherine N, Kabbaj, Mohamed
Abstract/Description: Only a portion of the population exposed to trauma will develop persistent emotional alterations characteristic of posttraumatic stress disorder (PTSD), which illustrates the necessity for identifying vulnerability factors and novel pharmacotherapeutic alternatives. Interestingly, clinical evidence suggests that novelty seeking is a good predictor for vulnerability to the development of excessive and persistent fear. Here, we first tested this hypothesis by analyzing contextual and cued fear...
Show moreOnly a portion of the population exposed to trauma will develop persistent emotional alterations characteristic of posttraumatic stress disorder (PTSD), which illustrates the necessity for identifying vulnerability factors and novel pharmacotherapeutic alternatives. Interestingly, clinical evidence suggests that novelty seeking is a good predictor for vulnerability to the development of excessive and persistent fear. Here, we first tested this hypothesis by analyzing contextual and cued fear responses of rats selected for their high (high responders, HR) or low (low responders, LR) exploration of a novel environment, indicator of novelty seeking. While HR and LR rats exhibited similar sensitivity to the shock and cued fear memory retention, fewer extinction sessions were required in HR than LR animals to reach extinction, indicating faster contextual and cued memory extinction. In a second part, we found an effective disruption of contextual fear reconsolidation by the N-methyl-d-aspartate receptor antagonist ketamine, associated with a down-regulation of early growth response 1 (Egr1) in the hippocampal CA1 area, and up-regulation of brain-derived neurotrophic factor (Bdnf) mRNA levels in the prelimbic and infralimbic cortices. Altogether, these data demonstrate a link between novelty seeking and conditioned fear extinction, and highlight a promising novel role of ketamine in affecting established fear memory.
Show less
Date Issued: 2016-10-01
Identifier: FSU_pmch_27343386, 10.1016/j.neuropharm.2016.06.022, PMC5017153, 27343386, 27343386, S0028-3908(16)30275-1
Format: Citation

Title: The neurobiology of pair bond formation, bond disruption, and social buffering.
Creator: Lieberwirth, Claudia, Wang, Zuoxin
Abstract/Description: Enduring social bonds play an essential role in human society. These bonds positively affect psychological, physiological, and behavioral functions. Here, we review the recent literature on the neurobiology, particularly the role of oxytocin and dopamine, of pair bond formation, bond disruption, and social buffering effects on stress responses, from studies utilizing the socially monogamous prairie vole (Microtus ochrogaster).
Date Issued: 2016-10-01
Identifier: FSU_pmch_27290660, 10.1016/j.conb.2016.05.006, PMC5072360, 27290660, 27290660, S0959-4388(16)30065-4
Format: Citation

Title: The role of ΔfosB in the medial preoptic area: Differential effects of mating and cocaine history..
Creator: McHenry, Jenna A, Robison, Christopher L, Bell, Genevieve A, Vialou, Vincent V, Bolaños-Guzmán, Carlos A, Nestler, Eric J, Hull, Elaine M
Abstract/Description: The transcription factor deltaFosB (ΔFosB) is induced in the nucleus accumbens (NAc) by repeated exposure to drugs of abuse and natural rewards. Less is known about its role in other brain areas. Here, we compared the effects of mating versus cocaine history on induction of ΔFosB in the medial preoptic area (MPOA), an integral site for reproductive behavior, and in the NAc. ΔFosB immunoreactivity (ir) was increased in the MPOA of previously naïve and experienced male rats that mated the day...
Show moreThe transcription factor deltaFosB (ΔFosB) is induced in the nucleus accumbens (NAc) by repeated exposure to drugs of abuse and natural rewards. Less is known about its role in other brain areas. Here, we compared the effects of mating versus cocaine history on induction of ΔFosB in the medial preoptic area (MPOA), an integral site for reproductive behavior, and in the NAc. ΔFosB immunoreactivity (ir) was increased in the MPOA of previously naïve and experienced male rats that mated the day before euthanasia, compared to unmated controls and experienced males with recent mating abstinence. Western immunoblots confirmed that the 35-37-kDa isoform of ΔFosB was increased more in recently mated males. Conversely, previous plus recent cocaine did not increase ΔFosB-ir in the MPOA, despite an increase in the NAc. Next, a viral vector expressing ΔFosB, its dominant negative antagonist ΔJunD, or green fluorescent protein (GFP) control, were microinjected bilaterally into the MPOA. ΔFosB overexpression impaired copulation and promoted female-directed aggression, compared to ΔJunD and control males. These data suggest that ΔFosB in the mPOA is expressed in an experience-dependent manner and affects systems that coordinate mating and aggression. (PsycINFO Database Record
Show less
Date Issued: 2016-10-01
Identifier: FSU_pmch_27657309, 10.1037/bne0000160, PMC5201202, 27657309, 27657309, 2016-45747-001
Format: Citation

Department of Biological Science (19)	+ -
Department of Psychology (16)	+ -
Department of Biomedical Sciences (14)	+ -
Institute of Molecular Biophysics (12)	+ -
Department of Mathematics (6)	+ -

Department of Chemistry and Biochemistry (3)	+ -
Center for Genomics and Personalized Medicine (2)	+ -
Department of Statistics (2)	+ -
Center for Brain Repair (1)	+ -
College of Medicine (1)	+ -
Department of Behavioral Sciences and Social Medicine (1)	+ -

Animals (42)	+ -
Male (22)	+ -
Female (15)	+ -
Mice (10)	+ -
Rats (9)	+ -

Humans (8)	+ -
Mice, Inbred C57BL (7)	+ -
Rats, Sprague-Dawley (7)	+ -
Disease Models, Animal (5)	+ -
Ketamine/pharmacology (4)	+ -
Neurons/physiology (4)	+ -
Pair Bond (4)	+ -
Social Behavior (4)	+ -
Analysis of Variance (3)	+ -
Arvicolinae/physiology (3)	+ -
Calcium/metabolism (3)	+ -
Cocaine/pharmacology (3)	+ -
Conditioning, Operant/drug effects (3)	+ -
Conditioning, Operant/physiology (3)	+ -
Hippocampus/physiology (3)	+ -
Immunohistochemistry (3)	+ -
Insulin/metabolism (3)	+ -
Locomotion/drug effects (3)	+ -
Memory, Long-Term/physiology (3)	+ -
Memory/drug effects (3)	+ -
Mice, Knockout (3)	+ -
Mice, Transgenic (3)	+ -
Neurons/metabolism (3)	+ -
Prefrontal Cortex/metabolism (3)	+ -
Time Factors (3)	+ -

text (66)	+ -
journal article (59)	+ -

Search In

Pages

Pages

Sort Results By:

Narrow results by:

Collection

Topical Subject

Genre

Type of Resource

Language

Creator

Found In

Owner