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Peptidergic modulation of thermoregulation and energy expenditure

温度调节和能量消耗的肽能调节

基本信息

批准号：
9318589
负责人：
Iustin Virgil Tabarean
金额：
$ 41.8万
依托单位：
SCINTILLON INSTITUTE FOR PHOTOBIOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9318589
关键词：
Address Anatomy Anterior Hypothalamus Arginine Arousal Biological Neural Networks Body Temperature Brain Brain Stem Brain region Cations Cell Nucleus Cells Characteristics Data Electrophysiology (science)Energy Metabolism Future Glutamates Goals Homeostasis Hyperthermia Image Infusion procedures Injectable Injection of therapeutic agent Ions Knowledge Label Ligands Light Maintenance Mammals Medial Mediating Motor Activity Mus Neurons Neuropeptide Receptor Neuropeptides Neurotensin Obesity Organism Output Pathway interactions Pattern Peptides Pharmacology Physiologic Thermoregulation Physiology Play Preoptic Areas Process Property Reporting Research Role Signal Pathway Signal Transduction Site Slice Synapses Telemetry Testing Therapeutic Thermogenesis Transgenic Model Transgenic Organisms Visceral diencephalon experimental study in vivo induced hypothermia medial preoptic nucleus natural hypothermia neuroregulation optogenetics public health relevance receptor response tool zona incerta

项目摘要

DESCRIPTION (provided by applicant): Zona incerta (ZI) of the diencephalon has extensive connections with other brain regions and has been involved in several functions such as controlling visceral activity, thermoregulation, arousal and locomotor activity. In spite of its important functions it is one of the most understudied regions of the brain and no studies of the cellular and synaptic electrophysiological properties of ZI neurons have been reported so far. Maintenance of body temperature is central to energy homeostasis in mammals because it represents a major part of the energy expenditure of the organism. It is controlled by neurons of the preoptic area/ anterior hypothalamus (PO/AH) that project directly or indirectly to the rostral raphe pallidus. Anatomical and functional evidence clearly indicate a projection from the preoptic area, the thermoregulatory center, to ZI neurons. Combined retrograde labeling/immunostaining experiments have revealed that preoptic neurons projecting to ZI are peptidergic. ZI neurons project to the raphe pallidus and thus they can represent a relay of the preoptic thermogenic output to the brainstem neurons controlling thermoeffector processes. Our overarching hypothesis is that ZI GABAergic neurons mediate the peptidergic modulation of thermoregulation by PO/AH neurons. Preliminary data indicate that ZI neurons express receptors for these neuropeptides. We have also found that thermoregulatory neuropeptides excite ZI GABAergic neurons by activating inward currents and that they increase intracellular Ca concentrations. Our preliminary data also show that preoptic neurons projecting to ZI GABAergic neurons are peptidergic. Using transgenic models and telemetry we plan to study the role of ZI neurons in mediating the modulation of thermoregulation by neuropeptides (Sp Aim 1). We plan to identify thermoregulatory ZI neurons in slices and study their firing and synaptic characteristics as well as their modulation by neuropeptides involved in thermoregulation, followed by single cell RT/PCR analysis to determine the expression patterns for these receptors (Sp. Aim 2). By employing pharmacological tools, Ca imaging, electrophysiology and transgenic models we will then study the signaling pathways and the ion conductances involved in the neuropeptides' actions on ZI neurons (Sp. Aim 3). In summary in this study we will address fundamental and unexplored aspects of neural control of thermoregulation.