ELECTROPHYSIOLOGY & PHARMACOLOGY OF SLEEP-WAKEFULNESS
ELECTROPHYSIOLOGY & PHARMACOLOGY OF SLEEP-WAKEFULNESS
批准号:
6627581
负责人:
MAHESH M THAKKAR
金额:
$13.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-01-04 至 2004-12-31
中文摘要
描述(申请人摘要):本计划的总体目标
研究是为了了解其生理和药理机制
控制睡眠,包括快速眼动阶段和非快速眼动阶段,从而提供声音
了解和治疗人类睡眠障碍的基础,两者
医学和精神疾病的主要和次要原因。这些实验
本建议书中描述的重点是了解睡眠和觉醒
在细胞水平上。要使用的关键技术是一种新的组合
自由活动猫的微透析和细胞外单单位记录。
非快速眼动睡眠阶段。尽管数据,包括我们实验室的数据,
提示腺苷是一种内源性睡眠因子,作用于大脑
促进睡眠的非快速眼动阶段,特定的细胞机制
腺苷的作用尚不清楚。腺苷的强大状态改变作用
主要通过基底前脑胆碱能神经元的广泛分布和
大脑皮质和丘脑系统的战略性传出投射
已知对控制大脑皮层的激活很重要。最基本的
前脑/前脑的视前区广泛与行为有关
国家控制。需要研究的主要假设是腺苷是否
通过选择性抑制脑区觉醒活性神经元介导睡眠效应
基底前脑/视前区,没有任何影响
非觉醒活动和/或睡眠相关神经元。我们目前的初步数据是
CAT支持这一假说,即大脑基底节区的觉醒活性神经元
前脑/视前区介导腺苷的催眠作用,
通过A1受体发挥作用。我们还将评估去甲肾上腺素能
对觉醒的基底前脑调节的控制。初步数据显示
去甲肾上腺素增加基底前脑的放电活动
唤醒活跃的神经元。
快速眼动睡眠阶段。去甲肾上腺素基因座假说
蓝斑神经元抑制胆碱能神经元并允许发生快速眼动睡眠
当这些蓝斑神经元在慢波和快速眼动时放慢放电
睡眠也将被评估。我们将检验蓝斑假说
通过α-2受体作用的输入抑制中脑桥核的放电
已被行为学鉴定为胆碱能区神经元
在快速眼动睡眠期间优先激活。相反,我们预测神经元活跃
在清醒状态和快速眼动状态下,睡眠受到的影响都很小或根本不受
去甲肾上腺素在微透析中的应用。最后,使用相同的单位
记录/微透析技术,我们将检查
5-羟色胺对中缝背核睡眠相关减慢的控制作用
通过5-HT1a体树突状受体的神经元放电。初步数据
提示微透析应用8-OH-DPAT具有较强的抑制作用。
中缝背核的状态相关放电活动,我们还将
研究5HT1A拮抗剂的作用。
英文摘要
DESCRIPTION (applicant's abstract): The broad objective of this program of
research is to understand the physiological and pharmacological mechanisms
controlling sleep, both the REM and nonREM phases, and thereby provide a sound
basis for the understanding and treatment of human sleep disorders, both
primary and secondary to medical and psychiatric conditions. The experiments
described in this proposal focus on understanding of sleep and wakefulness at
the cellular level. The key technique to be used is a novel combination of
microdialysis and extracellular single unit recording in freely behaving cats.
The nonREM sleep phase. Although data, including those from our laboratory,
suggest adenosine is an endogenous sleep factor that acts on the brain to
promote the nonREM phase of sleep, the specific cellular mechanisms of
adenosine's actions are not known. Adenosine's powerful state-altering effects
occur primarily via the basal forebrain cholinergic neurons' widespread and
strategic efferent projections to the cortical and thalamic systems that are
known to be important for the control of cortical activation. The basal
forebrain/preoptic region of the forebrain is widely implicated in behavioral
state control. The major hypothesis to be investigated is whether adenosine
mediates sleep effect by the selective inhibition of the wake-active neurons in
the basal forebrain/preoptic region, without having any effect of
non-wake-active and/or sleep-related neurons. Our present preliminary data in
cat support the hypothesis that the wake-active neurons of the basal
forebrain/preoptic region mediate the sleep-promoting actions of adenosine,
acting via A1 receptors. We will also evaluate the extent of noradrenergic
control on the basal forebrain regulation of arousal. Preliminary data indicate
that norepinephrine increases the discharge activity of basal forebrain
wake-active neurons.
The REM sleep phase. The hypothesis that norepinephrine-containing locus
coeruleus neurons disinhibit cholinergic neurons and allow REM sleep to occur
when these locus coeruleus neurons slow discharge during slow wave and REM
sleep will also be evaluated. We will test the hypothesis the locus coeruleus
input acting through the alpha-2 receptor inhibits discharge of the mesopontine
cholinergic zone neurons that have been behaviorally identified to be
preferentially active during REM sleep. In contrast, we predict neurons active
in both wakefulness and REM sleep will be minimally or not at all affected by
microdialysis application of norepinephrine. Finally, using the same unit
recording/microdialysis technique, we will examine the degree to which
serotonin acts to control the sleep-related slowing of dorsal raphe nucleus
neuronal discharge via the 5-HT1A somato-dendritic receptors. Preliminary data
suggest a strong suppressive effect of microdialysis-applied 8-OH-DPAT on
state-related discharge activity of the dorsal raphe nucleus, and we will also
investigate the effects of 5HT1A antagonists.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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