Xiao-Bing Gao, PhD
Research & Publications
Biography
News
Research Summary
The lateral hypothalamus (LH) plays a substantial role in a number of functions including sensorimotor integration, energy homeostasis, sleep-wake regulation, addiction, emotion and regulation of the autonomic nervous system. It has been shown that the LH is a central hub receiving physiological, behavioral and environmental inputs from and sending outputs to other brain structures to participate in homeostatic and behavioral functions. Our long-term goal is to understand how signaling at molecular, cellular and systems levels leads to the emergence of instinctive behaviors critical for animal survival and how adaptive and maladaptive changes in the LH lead to diseases and conditions such as obesity, diabetes, sleep disorders, etc.
Specialized Terms: Neurotransmission; Neurotransmitter response and synaptic plasticity; Cellular physiology of neuropeptides (hypocretin/orexin, melanin concentrating hormone, neuropeptide Y, ghrelin, leptin, and a-MSH); Ion channels (Na+, Ca2+, K+ channels); Electrophysiology/patch clamp recording; calcium imaging; Hypothalamus/lateral hypothalamic area; Energy homeostasis/feeding regulation; Sleep homeostasis and regulation; Drug addiction
Extensive Research Description
The lateral hypothalamus (LH) plays a substantial role in a number of functions including sensorimotor integration, energy homeostasis, sleep-wake regulation, addiction, emotion and regulation of the autonomic nervous system. It has been shown that the LH is a central hub receiving physiological, behavioral and environmental inputs from and sending outputs to other brain structures to participate in homeostatic and behavioral functions.
Despite its critical role in the survival of individuals and species, it is largely unclear how the LH integrates information from internal and external environments to exert its actions. Moreover, it is also not clear how the neural circuitry centered on neurons in the LH make adaptive changes to accommodate physiological, behavioral and environmental changes. Our long-term goal is to understand the logic of how signaling at molecular, cellular and circuit levels leads to the emergence of instinctive behaviors critical for animal survival.
Specifically, the questions that we are pursuing include: 1) how neural circuitry in the LH participates in the regulation of homeostatic and behavioral functions of the brain; 2) how neural circuitry in the LH is modified by physiological, behavioral and environmental changes in mature animals; 3) how maternal and early postnatal experience leads to changes in the development of neural circuitry responsible for dysfunctions of the LH during adulthood.
1. Hypocretinergic control of drug addiction
The long-term goal of this proposal is to bridge the gap between clinical studies and basic research on the role of the hypocretin system in cocaine addiction-related behaviors in animals. Supported by NIH/NIDA
2. MCHergic control of feeding and energy balance
In this project we propose to identify interactions between MCH neurons and hypocretin neurons in the lateral hypothalamus in the regulation of feeding behavior and energy balance in mice. Supported by NIH/NIDDK
Coauthors
Research Interests
Action Potentials; Anorexia Nervosa; Anxiety; Electrophysiology; Food Deprivation; Hypothalamus; Ion Channels; Membrane Potentials; Synaptic Transmission; Neuronal Plasticity; Neurophysiology; Obesity; Sleep Deprivation; Sleep Wake Disorders; Glutamic Acid; Synaptic Potentials; Food Addiction
Public Health Interests
Obesity; Substance Use, Addiction
Research Image
The cross-talk among neurons in the lateral hypothalamus
Selected Publications
- Response to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effectTakahashi T, Stoiljkovic M, Song E, Gao X, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu Z, Kristant A, Zhang Y, Sulkowski P, Glazer P, Kaczmarek L, Horvath T, Iwasaki A. Response to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect Neuron 2023, 111: 612-613. PMID: 36863323, DOI: 10.1016/j.neuron.2023.02.006.
- Impaired hypocretin/orexin system alters responses to salient stimuli in obese male miceTan Y, Hang F, Liu ZW, Stoiljkovic M, Wu M, Tu Y, Han W, Lee AM, Kelley C, Hajos M, Lu L, de Lecea L, de Araujo I, Picciotto M, Horvath TL, Gao XB. Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice Journal Of Clinical Investigation 2020, 130: 4985-4998. PMID: 32516139, PMCID: PMC7456212, DOI: 10.1172/jci130889.
- A step towards the automation of intracytoplasmic sperm injection (ICSI): real time confirmation of oocyte penetration by electrical resistance measurementMor A, Zhang M, Esencan E, Simsek B, Nichols-Burns S, Liu Y, Lo J, Kelk D, Gao X, Seli E. A step towards the automation of intracytoplasmic sperm injection (ICSI): real time confirmation of oocyte penetration by electrical resistance measurement Fertility And Sterility 2019, 112: e90-e91. DOI: 10.1016/j.fertnstert.2019.07.357.
- Critical role of Lin28‐TNFR2 signalling in cardiac stem cell activation and differentiationXiang Q, Yang B, Li L, Qiu B, Qiu C, Gao X, Zhou H, Min W. Critical role of Lin28‐TNFR2 signalling in cardiac stem cell activation and differentiation Journal Of Cellular And Molecular Medicine 2019, 23: 0-0. PMID: 30734494, PMCID: PMC6433861, DOI: 10.1111/jcmm.14202.
- The Role of Melanin-Concentrating Hormone in the Regulation of the Sleep/Wake Cycle: Sleep Promoter or Arousal Modulator?Gao X. The Role of Melanin-Concentrating Hormone in the Regulation of the Sleep/Wake Cycle: Sleep Promoter or Arousal Modulator? 2018, 57-74. DOI: 10.1007/978-3-319-75765-0_3.
- Endometriosis alters anxiety, depression and pain perception as well as brain electrophysiology and gene expression in miceMamillapalli R, Gao X, Taylor H. Endometriosis alters anxiety, depression and pain perception as well as brain electrophysiology and gene expression in mice Fertility And Sterility 2017, 108: e43-e44. DOI: 10.1016/j.fertnstert.2017.07.142.
- Neural plasticity in hypocretin neurons: the basis of hypocretinergic regulation of physiological and behavioral functions in animalsGao XB, Hermes G. Neural plasticity in hypocretin neurons: the basis of hypocretinergic regulation of physiological and behavioral functions in animals Frontiers In Systems Neuroscience 2015, 9: 142. PMID: 26539086, PMCID: PMC4612503, DOI: 10.3389/fnsys.2015.00142.
- Repeated in vivo exposure of cocaine induces long‐lasting synaptic plasticity in hypocretin/orexin‐producing neurons in the lateral hypothalamus in miceRao Y, Mineur YS, Gan G, Wang AH, Liu Z, Wu X, Suyama S, de Lecea L, Horvath TL, Picciotto MR, Gao X. Repeated in vivo exposure of cocaine induces long‐lasting synaptic plasticity in hypocretin/orexin‐producing neurons in the lateral hypothalamus in mice The Journal Of Physiology 2013, 591: 1951-1966. PMID: 23318871, PMCID: PMC3624862, DOI: 10.1113/jphysiol.2012.246983.
- Erratum: CORRIGENDUM: Fetal Radiofrequency Radiation Exposure From 800-1900 Mhz-Rated Cellular Telephones Affects Neurodevelopment and Behavior in MiceAldad T, Gan G, Gao X, Taylor H. Erratum: CORRIGENDUM: Fetal Radiofrequency Radiation Exposure From 800-1900 Mhz-Rated Cellular Telephones Affects Neurodevelopment and Behavior in Mice Scientific Reports 2013, 3: 1320. PMCID: PMC3575011, DOI: 10.1038/srep01320.
- Erratum: Corrigendum: Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesityDiano S, Liu Z, Jeong J, Dietrich M, Ruan H, Kim E, Suyama S, Kelly K, Gyengesi E, Arbiser J, Belsham D, Sarruf D, Schwartz M, Bennett A, Shanabrough M, Mobbs C, Yang X, Gao X, Horvath T. Erratum: Corrigendum: Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity Nature Medicine 2011, 17: 1320-1320. DOI: 10.1038/nm1011-1320a.
- Intracellular energy status regulates activity in hypocretin/orexin neurones: a link between energy and behavioural statesLiu Z, Gan G, Suyama S, Gao X. Intracellular energy status regulates activity in hypocretin/orexin neurones: a link between energy and behavioural states The Journal Of Physiology 2011, 589: 4157-4166. PMID: 21727218, PMCID: PMC3180576, DOI: 10.1113/jphysiol.2011.212514.
- Endometrial stem cell transplantation restores dopamine production in a Parkinson’s disease modelWolff EF, Gao X, Yao KV, Andrews ZB, Du H, Elsworth JD, Taylor HS. Endometrial stem cell transplantation restores dopamine production in a Parkinson’s disease model Journal Of Cellular And Molecular Medicine 2011, 15: 747-755. PMID: 20406327, PMCID: PMC2998585, DOI: 10.1111/j.1582-4934.2010.01068.x.
- Direct Evidence for Wake-Related Increases and Sleep-Related Decreases in Synaptic Strength in Rodent CortexLiu ZW, Faraguna U, Cirelli C, Tononi G, Gao XB. Direct Evidence for Wake-Related Increases and Sleep-Related Decreases in Synaptic Strength in Rodent Cortex Journal Of Neuroscience 2010, 30: 8671-8675. PMID: 20573912, PMCID: PMC2903226, DOI: 10.1523/jneurosci.1409-10.2010.
- Experience‐dependent plasticity in hypocretin/orexin neurones: re‐setting arousal thresholdGao X, Wang AH. Experience‐dependent plasticity in hypocretin/orexin neurones: re‐setting arousal threshold Acta Physiologica 2009, 198: 251-262. PMID: 19785627, PMCID: PMC2860674, DOI: 10.1111/j.1748-1716.2009.02047.x.
- Erratum: UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicalsAndrews Z, Liu Z, Walllingford N, Erion D, Borok E, Friedman J, Tschöp M, Shanabrough M, Cline G, Shulman G, Coppola A, Gao X, Horvath T, Diano S. Erratum: UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals Nature 2009, 459: 736-736. DOI: 10.1038/nature08132.
- Regulation of Synaptic Efficacy in Hypocretin/Orexin-Containing Neurons by Melanin Concentrating Hormone in the Lateral HypothalamusRao Y, Lu M, Ge F, Marsh DJ, Qian S, Wang AH, Picciotto MR, Gao XB. Regulation of Synaptic Efficacy in Hypocretin/Orexin-Containing Neurons by Melanin Concentrating Hormone in the Lateral Hypothalamus Journal Of Neuroscience 2008, 28: 9101-9110. PMID: 18784290, PMCID: PMC2562258, DOI: 10.1523/jneurosci.1766-08.2008.
- Human Endometrial Stem Cells Transplantation in a Parkinson's Disease Mouse Model.Wolff E, Gao X, Andrews Z, Yao K, Du H, Taylor H. Human Endometrial Stem Cells Transplantation in a Parkinson's Disease Mouse Model. Biology Of Reproduction 2008, 78: 120-120. DOI: 10.1093/biolreprod/78.s1.120d.
- Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons.Rao Y, Liu ZW, Borok E, Rabenstein RL, Shanabrough M, Lu M, Picciotto MR, Horvath TL, Gao XB. Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons. Journal Of Clinical Investigation 2007, 117: 4022-33. PMID: 18060037, PMCID: PMC2104495, DOI: 10.1172/jci32829.
- Adenosine Inhibits Activity of Hypocretin/Orexin Neurons by the A1 Receptor in the Lateral Hypothalamus: A Possible Sleep-Promoting EffectLiu ZW, Gao XB. Adenosine Inhibits Activity of Hypocretin/Orexin Neurons by the A1 Receptor in the Lateral Hypothalamus: A Possible Sleep-Promoting Effect Journal Of Neurophysiology 2006, 97: 837-848. PMID: 17093123, PMCID: PMC1783688, DOI: 10.1152/jn.00873.2006.
- Input organization and plasticity of hypocretin neurons Possible clues to obesity’s association with insomniaHorvath TL, Gao XB. Input organization and plasticity of hypocretin neurons Possible clues to obesity’s association with insomnia Cell Metabolism 2005, 1: 279-286. PMID: 16054072, DOI: 10.1016/j.cmet.2005.03.003.
- Hypocretin/Orexin Excites Hypocretin Neurons via a Local Glutamate Neuron—A Potential Mechanism for Orchestrating the Hypothalamic Arousal SystemLi Y, Gao X, Sakurai T, van den Pol AN. Hypocretin/Orexin Excites Hypocretin Neurons via a Local Glutamate Neuron—A Potential Mechanism for Orchestrating the Hypothalamic Arousal System Neuron 2002, 36: 1169-1181. PMID: 12495630, DOI: 10.1016/s0896-6273(02)01132-7.
- Melanin‐concentrating hormone depresses L‐, N‐, and P/Q‐type voltage‐dependent calcium channels in rat lateral hypothalamic neuronsGao X, Pol A. Melanin‐concentrating hormone depresses L‐, N‐, and P/Q‐type voltage‐dependent calcium channels in rat lateral hypothalamic neurons The Journal Of Physiology 2002, 542: 273-286. PMID: 12096069, PMCID: PMC2290404, DOI: 10.1113/jphysiol.2002.019372.
- Hypocretin (orexin) enhances neuron activity and cell synchrony in developing mouse GFP‐expressing locus coeruleusPol A, Ghosh PK, Liu R, Li Y, Aghajanian GK, Gao X. Hypocretin (orexin) enhances neuron activity and cell synchrony in developing mouse GFP‐expressing locus coeruleus The Journal Of Physiology 2002, 541: 169-185. PMID: 12015428, PMCID: PMC2290314, DOI: 10.1113/jphysiol.2002.017426.
- Membrane Properties Underlying Patterns of GABA-Dependent Action Potentials in Developing Mouse Hypothalamic NeuronsWang Y, Gao X, van den Pol A. Membrane Properties Underlying Patterns of GABA-Dependent Action Potentials in Developing Mouse Hypothalamic Neurons Journal Of Neurophysiology 2001, 86: 1252-1265. PMID: 11535674, DOI: 10.1152/jn.2001.86.3.1252.
- Lateral hypothalamus: Early developmental expression and response to hypocretin (orexin)Van Den Pol A, Patrylo P, Ghosh P, Gao X. Lateral hypothalamus: Early developmental expression and response to hypocretin (orexin) The Journal Of Comparative Neurology 2001, 433: 349-363. PMID: 11298360, DOI: 10.1002/cne.1144.
- Melanin concentrating hormone depresses synaptic activity of glutamate and GABA neurons from rat lateral hypothalamusGao X, Pol A. Melanin concentrating hormone depresses synaptic activity of glutamate and GABA neurons from rat lateral hypothalamus The Journal Of Physiology 2001, 533: 237-252. PMID: 11351031, PMCID: PMC2278620, DOI: 10.1111/j.1469-7793.2001.0237b.x.
- GABA, Not Glutamate, a Primary Transmitter Driving Action Potentials in Developing Hypothalamic NeuronsGao X, Van Den Pol A. GABA, Not Glutamate, a Primary Transmitter Driving Action Potentials in Developing Hypothalamic Neurons Journal Of Neurophysiology 2001, 85: 425-434. PMID: 11152743, DOI: 10.1152/jn.2001.85.1.425.
- GABA release from mouse axonal growth conesGao X, Pol A. GABA release from mouse axonal growth cones The Journal Of Physiology 2000, 523: 629-637. PMID: 10718743, PMCID: PMC2269824, DOI: 10.1111/j.1469-7793.2000.t01-1-00629.x.
- Kainate Acts at Presynaptic Receptors to Increase GABA Release From Hypothalamic NeuronsLiu Q, Patrylo P, Gao X, van den Pol A. Kainate Acts at Presynaptic Receptors to Increase GABA Release From Hypothalamic Neurons Journal Of Neurophysiology 1999, 82: 1059-1062. PMID: 10444697, DOI: 10.1152/jn.1999.82.2.1059.
- Neurotrophin‐3 potentiates excitatory GABAergic synaptic transmission in cultured developing hypothalamic neurones of the ratGao X, Pol A. Neurotrophin‐3 potentiates excitatory GABAergic synaptic transmission in cultured developing hypothalamic neurones of the rat The Journal Of Physiology 1999, 518: 81-95. PMID: 10373691, PMCID: PMC2269394, DOI: 10.1111/j.1469-7793.1999.0081r.x.
- Glutamate Inhibits GABA Excitatory Activity in Developing Neuronsvan den Pol A, Gao X, Patrylo P, Ghosh P, Obrietan K. Glutamate Inhibits GABA Excitatory Activity in Developing Neurons Journal Of Neuroscience 1998, 18: 10749-10761. PMID: 9852609, PMCID: PMC6793361, DOI: 10.1523/jneurosci.18-24-10749.1998.
- Presynaptic and Postsynaptic Actions and Modulation of Neuroendocrine Neurons by a New Hypothalamic Peptide, Hypocretin/Orexinvan den Pol A, Gao X, Obrietan K, Kilduff T, Belousov A. Presynaptic and Postsynaptic Actions and Modulation of Neuroendocrine Neurons by a New Hypothalamic Peptide, Hypocretin/Orexin Journal Of Neuroscience 1998, 18: 7962-7971. PMID: 9742163, PMCID: PMC6793026, DOI: 10.1523/jneurosci.18-19-07962.1998.
- GABA-Dependent Firing of Glutamate-Evoked Action Potentials at AMPA/Kainate Receptors in Developing Hypothalamic NeuronsGao X, Chen G, van den Pol A. GABA-Dependent Firing of Glutamate-Evoked Action Potentials at AMPA/Kainate Receptors in Developing Hypothalamic Neurons Journal Of Neurophysiology 1998, 79: 716-726. PMID: 9463435, DOI: 10.1152/jn.1998.79.2.716.
- The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activityde Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg E, Gautvik VT, Bartlett FS, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG. The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 322-327. PMID: 9419374, PMCID: PMC18213, DOI: 10.1073/pnas.95.1.322.