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Electrophysiology of zona incerta neurons

未定带神经元的电生理学

基本信息

批准号：
8739989
负责人：
Iustin Virgil Tabarean
金额：
$ 47.38万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-30 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8739989
关键词：
Address Anterior Hypothalamus Area Arginine Argipressin Arousal Biological Neural Networks Body Temperature Brain Brain Stem Brain region Cell Nucleus Cells Characteristics Data Development Disease Electrophysiology (science)Energy Metabolism Future Glutamates Goals Homeostasis Hyperthermia Image Infection Infusion procedures Injection of therapeutic agent Ions Knowledge Label Ligands Maintenance Mammals Medial Mediating Motor Activity Mus Neurons Neuropeptide Receptor Neuropeptides Neurotensin Obesity Organism Output Pathway interactions Pattern Peptides Peripheral Physiologic Thermoregulation Physiology Play Preoptic Areas Process Property Reporting Research Reverse Transcriptase Polymerase Chain Reaction Role Signal Pathway Signal Transduction Site Slice Synapses Telemetry Testing Therapeutic Thermogenesis Visceral diencephalon in vivo induced hypothermia natural hypothermia neurophysiology public health relevance receptor research study response small hairpin RNA 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 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 preoptic neurons. Preliminary data indicate that ZI neurons express receptors for these neuropeptides. We have also found that thermoregulatory neuropeptides excites 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. We plan to identify both GABAergic and glutamatergic 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. aim1). A set of experiments will utilize retrograde labeling from the raphe pallidus to identify ZI neurons projecting to that area. By employing pharmacological tools, Ca imaging, electrophysiology and single cell RT-PCR we will then study the signaling pathways and the ion conductances involved in the neuropeptides' actions on ZI neurons (Sp. Aim2). In Sp Aim 3 we will determine using telemetry and local infusions of pharmacological agents the role of AVP and neurotensin signaling in the ZIv in thermoregulation. Studying the cellular mechanisms and signaling pathways activated by thermoregulatory peptides in ZI neurons may provide central pharmacological targets for the development of hypothermic agents and for the control of energy homeostasis. In summary in this study we will address fundamental and unexplored aspects of neurophysiology and start to lay the groundwork for understanding the role of perturbed peptidergic signaling to disease.

描述（申请人提供）：间脑内隐带（ZI）与大脑其他区域有广泛的联系，参与控制内脏活动、体温调节、觉醒和运动活动等多种功能。尽管它具有重要的功能，但它是大脑中研究最少的区域之一，迄今为止还没有关于ZI神经元的细胞和突触电生理特性的研究报道。体温的维持是哺乳动物能量稳态的核心，因为它代表了生物体能量消耗的主要部分。它由直接或间接投射到吻侧的视前区/下丘脑前部（PO/AH）神经元控制