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(申请人的摘要):本计划的广泛目标是
研究是为了了解生理和药理机制
控制睡眠,REM和非REM阶段,从而提供声音
了解和治疗人类睡眠障碍的基础,
主要和次要的医疗和精神状况。实验
在这个建议中描述的重点是了解睡眠和觉醒,
细胞水平。要使用的关键技术是一种新的组合,
微透析和细胞外单个单位记录在自由行为的猫。
非REM睡眠阶段尽管数据,包括我们实验室的数据,
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,
腺苷的作用尚不清楚。腺苷强大的状态改变作用
主要通过基底前脑胆碱能神经元的广泛和
向皮质和丘脑系统的战略传出投射,
已知对控制皮层激活很重要。基底
前脑/前脑的视前区广泛涉及行为
国家控制。待研究的主要假设是腺苷是否
通过选择性抑制脑内的觉醒神经元介导睡眠效应,
基底前脑/视前区,没有任何影响,
非唤醒活跃和/或睡眠相关神经元。我们目前的初步数据,
猫支持这一假设,即唤醒活跃的神经元的基底
前脑/视前区介导腺苷的睡眠促进作用,
通过A1受体起作用。我们还将评估去甲肾上腺素能
控制基底前脑对觉醒的调节。初步数据显示
去甲肾上腺素增加基底前脑的放电活动
唤醒活跃神经元。
REM睡眠阶段假设含有去甲肾上腺素的位点
蓝斑神经元解除胆碱能神经元的抑制,并允许REM睡眠发生
当这些蓝斑神经元在慢波和REM期间减慢放电时,
睡眠也将被评估。我们将检验蓝斑
通过α-2受体作用的输入抑制中脑脑桥的放电
胆碱能区神经元已被行为学鉴定为
在快速眼动睡眠时更活跃。相反,我们预测神经元活跃
在清醒和快速眼动睡眠中,
去甲肾上腺素的微透析应用。最后,使用相同的单位
记录/微透析技术,我们将检查
5-羟色胺控制睡眠相关的中缝背核减慢
通过5-HT 1A体细胞-树突受体的神经元放电。初步数据
表明微透析应用8-OH-DPAT对
状态相关的放电活动中缝背核,我们也将
研究5 HT 1A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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