SLEEP CONTROL BY THERMOSENSITIVE NEURONS

热敏神经元控制睡眠

• 批准号: 6771070
• 负责人: DENNIS J MCGINTY
• 金额: $ 22.05万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6771070
• 关键词: REM sleep; body temperature; body temperature regulation; brain electrical activity; dorsal raphe nucleus; electroencephalography; gamma aminobutyrate; hypothalamus; microdialysis; neurophysiology; neurotransmitter transport; prosencephalon; sleep; sleep deprivation; sleep disorders; sleep regulatory center; thermometry

DESCRIPTION (applicant's abstract): We propose to study neurophysiological mechanisms mediating the regulation of serotonin-containing neurons in the mammalian dorsal raphe nucleus (DRN) by the hypnogenic system in the preoptic hypothalamus and adjacent basal forebrain (POA/BF). Activation during spontaneous sleep of warm-sensitive neurons (WSNs) and deactivation of cold-sensitive neurons (CSNs) plays a critical role in the POA/BF hypnogenic process. WSNs and CSNs are identified by responses to local warming and cooling. Previous evidence shows that the POA/BF also contains both REM-facilitatory and REM-inhibitory processes. Suppression of DRN serotonergic neuronal discharge was shown to play a role in both NREM sleep onset and REM sleep triggering. Recent anatomical and physiological evidence shows that activation of the POA/BF WSN/CSN hypnogenic system can induce suppression of DRN neuronal activity, suggesting a mechanistic basis for NREM-REM coordination. We have developed a testable 2-stage model of regulation of DRN and REM triggering by the POA/BF. Aim 1 is to quantify the regulation of REM sleep control by POA/BF temperature-sensitive neurons. Aim 2 is to use microdialysis to confirm that POA/BF warming induces increased release of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) in DRN, and that postsynaptic blockade of GABA in DRN prevents POA/BF-induced changes in NREM EEG deactivation and REM-triggering. Aim 3 will combine microdialysis and neuronal unit recording in the DRN to assess hypotheses that GABA release induced by POA/BF warming regulates DRN neuronal discharge and that DRN neuronal discharge regulates REM triggering. Aim 4 will use techniques to generate REM-enriched sleep and the method of proto-oncogene c-fos expression to label neuronal activity in order to assess a hypothesis that a subregion of the POA/BF, the peri-ventrolateral preoptic area (peri-VLPO) contains REM-selective neurons. Aim 5 is confirm the existence of REM-selective neurons in peri-VLPO using chronic neuronal unit recording techniques. Aim 6 is to use microdialysis of a GABA agonist, muscimol, to inactivate the peri-VLPO area to assess the hypothesis that this region is essential for REM-triggering. These studies will provide a new model of interactions of NREM and REM sleep mechanisms and will contribute to the understanding of human diseases including narcolepsy and affective disorder in which NREM-REM coupling is disordered.

描述（申请人摘要）：我们建议研究神经生理学 介导调节含降钙素神经元的机制 视前区催眠系统对哺乳动物中缝背核的影响 下丘脑和相邻基底前脑（POA/BF）。期间激活 温敏神经元（WSNs）自发睡眠和 冷敏感神经元（CSNs）在POA/BF催眠中起重要作用 过程WSNs和CSNs通过对局部变暖的响应来识别， 降温以前的证据表明，POA/BF也含有这两种物质， 快速眼动易化和抑制过程。抑制DRN神经递质 神经元放电被证明在NREM睡眠开始和REM中起作用 睡眠触发最近的解剖学和生理学证据表明， POA/BF WSN/CSN催眠系统的激活可以诱导抑制 DRN神经元活动，提示NREM-REM的机制基础 协同我们开发了一个可检验的DRN调节的两阶段模型 以及由POA/BF触发的REM。目的1是量化REM的调节 POA/BF温度敏感神经元控制睡眠。目标2：使用 微透析，以证实POA/BF加温诱导增加的 DRN中的抑制性神经递质γ-氨基丁酸（GABA）， DRN中GABA的突触后阻断防止POA/BF诱导的NREM变化 脑电图失活和快速眼动触发Aim 3将联合收割机和 DRN中的神经元单位记录，以评估GABA释放 POA/BF加温引起的DRN神经元放电调节， 神经元放电调节REM触发。Aim 4将使用技术来 产生REM-丰富睡眠和原癌基因c-fos表达的方法 标记神经元活动，以评估一个假设， POA/BF，腹外侧视前区周围（peria-ventrolateral preoptic area，peria-VLPO）， REM选择性神经元目的5是证实REM选择性神经元的存在 使用慢性神经元单位记录技术。目标6是使用 GABA激动剂蝇蕈醇的微透析，以使VLPO周围区域 评估这一区域对REM触发至关重要的假设。这些 研究将提供一个新的模型，NREM和REM睡眠的相互作用， 机制，并将有助于了解人类疾病，包括 发作性睡病和其中NREM-REM耦合紊乱的情感障碍。

项目成果

Effects of lateral preoptic area application of orexin-A on sleep-wakefulness.

外侧视前区应用食欲素-A 对睡眠-觉醒的影响。

• DOI: 10.1097/00001756-200011090-00004
• 发表时间: 2000
• 期刊: Neuroreport
• 影响因子: 1.7
• 作者: Methippara,MM;Alam,MN;Szymusiak,R;McGinty,D
• 通讯作者: McGinty,D

Preoptic hypothalamic warming suppresses laryngeal dilator activity during sleep.

视前下丘脑变暖抑制睡眠期间喉部扩张器的活动。

• DOI: 10.1152/ajpregu.00296.2003
• 发表时间: 2004
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: McGinty,Dennis;Metes,Agnes;Alam,MdNoor;Megirian,David;Stewart,Darya;Szymusiak,Ron
• 通讯作者: Szymusiak,Ron

Thermosensitive neurons of the diagonal band in rats: relation to wakefulness and non-rapid eye movement sleep.

大鼠对角线带的热敏神经元：与觉醒和非快速动眼睡眠的关系。

• DOI: 10.1016/s0006-8993(96)01452-7
• 发表时间: 1997
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Alam,MN;McGinty,D;Szymusiak,R
• 通讯作者: Szymusiak,R

Hypothalamic sleep-promoting mechanisms: coupling to thermoregulation.

下丘脑睡眠促进机制：与体温调节的耦合。

• 发表时间: 2001
• 期刊: Archives italiennes de biologie
• 影响因子: 1
• 作者: McGinty,D;Alam,MN;Szymusiak,R;Nakao,M;Yamamoto,M
• 通讯作者: Yamamoto,M

Role of adenosine A(1) receptor in the perifornical-lateral hypothalamic area in sleep-wake regulation in rats.

• DOI: 10.1016/j.brainres.2009.09.066
• 发表时间: 2009-12-22
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Alam MN;Kumar S;Rai S;Methippara M;Szymusiak R;McGinty D
• 通讯作者: McGinty D