SYNAPTIC BASIS OF SLEEP CYCLE CONTROL
SYNAPTIC BASIS OF SLEEP CYCLE CONTROL
批准号:
6186455
负责人:
Robert W McCarley
金额:
$38.76万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1984
资助国家:
美国
项目状态:
已结题
起止时间:
1984-09-30 至 2002-04-30
关键词:
REM sleep acetylcholine adenosine biocytin brain electrical activity cats dorsal raphe nucleus electroencephalography electromyography electrooculography hypothalamus laboratory rat microdialysis neuropharmacology preoptic areas prosencephalon serotonin receptor sleep sleep regulatory center stereotaxic techniques wakefulness
中文摘要
这一系列研究的主要目的是利用动物实验来
英文摘要
The broad purpose of this series of studies is to use work in animals to
understand the physiological and pharmacological mechanism
controlling sleep, and thereby provide a sound baiss for the
understanding and treatment of human sleep disorders, both primary
and secondard to medical and physchiatric conditions. Previous work
has greatly advanced our knowledge of brainstem mechanisms
controlling the rapid eye movement (REM) phase of sleep, suggesting
that brainstem neurons using acetylcholine as a neurotransmitter
(cholinergic neurons) promote this phase of sleep. This application
builds on, and extends this work. The key techniques to be used are a
novel combination of microdialysis and extramcellular unit recording
in freely moving cats, intracellular recordings in naturally sleeping cats
and the rat in vitro slice preparation.
Hypotheses to be investigated include whether increases in adenosine
following prolonged wakefulness (and increased etabolic activity) act
as a factor reducing wakefulness (W) and increasing the Slow Wave
Sleep (SWS or nonREM) phase of sleep. We hypothesize adenosine
increases act most strongly on cholinergic neurons in the basal
forebrain and the mesopontine area that promote W and an activated
electroencephalogram (EEG). New data suggest strong adenosine
state-altering effects on the dorsal raphe nucleus (DRN) also.
Microdialysis measurements of extracellular adenosine and delivery of
adenosine transport inhibitors and concomitant unit recordings will be
used for in vivo tests, while in vitro studies will examine mechanisms
of action.
The hypothesis that serotonin-containing DRN neurons disinhibit
cholinergic neurons and allow REM sleep to occur when these DRN
neurons slow discharge during SWS and REM will also be evaluated;
in vivo and in vitro techniques will examine the degree to which each
of four factors may control the slowing of DRN discharge: GABA,
5HT collateral feedback, adenosine, and presynaptic disfacilitation of
adrenergic input. We will use intracellular in vivo recording and
double labeling to determine if the REM-on neurons (=discharge
activity selective for REM sleep, and possibly controlling this state)
and the Waking- and REM-on neurons (W/R-on, possibly controlling
EEG activation in both W and REM) recorded in the mesopontine
cholinergic zone can be positively identified as cholinergic. Using
microdialysis and unit recording we will test the hypothesis that the
REM-on neurons of this cholinergic zone differ from W/R-on neurons
by their inhibtability by DRN input acting on 5HT1A receptors.
Finally we will examine the Ventrolateral preoptic Area (VLPOA) of
hypothalamus, where earlier work with cFos protein indicated a
selective activation of a population of neurons during SWS. Using
microdialysis (MD) we will evaluate whether spontaneous extracellular
GABA levels decrease during SWS, suggesting disinhibition, and
whether MD-perfused bicuculline promotes SWS, as it did in
preliminary data. We will also evaluate the extent of cholinergic
control (from basal forebrain) and of histaminergic control (from the
tuberomammillary nucleus). In vitro work will examine the post- and
pre-synaptic effects of these and other neurotransmitters on VLPOA
neurons identified with biocytin and GAD immunohistochemical
labeling.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Basal Forebrain Cellular Mechanisms of Cortical Activation
-
批准号:8242210
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2011
-
负责人:Robert W McCarley
-
依托单位:
Basal Forebrain Cellular Mechanisms of Cortical Activation
-
批准号:8413399
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2011
-
负责人:Robert W McCarley
-
依托单位:
Basal Forebrain Cellular Mechanisms of Cortical Activation
-
批准号:8598052
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2011
-
负责人:Robert W McCarley
-
依托单位:
PROJECT 3: ELECTROPHYSIOLOGICAL & GRAY MATTER MARKERS & PREDICTORS OF PROGRESSION
-
批准号:8136028
-
项目类别:
-
资助金额:$12.53万
-
财政年份:2010
-
负责人:Robert W McCarley
-
依托单位:
CORE 1: OPERATIONS AND CLINICAL ASSESSMENT
-
批准号:8136030
-
项目类别:
-
资助金额:$24.09万
-
财政年份:2010
-
负责人:Robert W McCarley
-
依托单位:
Project 3 HMS - VA sub
-
批准号:9304306
-
项目类别:
-
资助金额:$31.21万
-
财政年份:2010
-
负责人:Robert W McCarley
-
依托单位:
Project 3 HMS - VA sub
-
批准号:8794523
-
项目类别:
-
资助金额:$33.06万
-
财政年份:2010
-
负责人:Robert W McCarley
-
依托单位:
MRI Anatomy of Schizophrenia
-
批准号:8586849
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2009
-
负责人:Robert W McCarley
-
依托单位:
MRI Anatomy of Schizophrenia
-
批准号:7906935
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2009
-
负责人:Robert W McCarley
-
依托单位:
Vulnerability to Progression Schizophrenia
-
批准号:7929313
-
项目类别:
-
资助金额:$30.5万
-
财政年份:2009
-
负责人:Robert W McCarley
-
依托单位:
MRI Anatomy of Schizophrenia
-
批准号:8195955
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2009
-
负责人:Robert W McCarley
-
依托单位:
Neurophysiological Studies of Schizophrenia
-
批准号:7809830
-
项目类别:
-
资助金额:$42.0万
-
财政年份:2009
-
负责人:Robert W McCarley
-
依托单位:
MRI Anatomy of Schizophrenia
-
批准号:7792783
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2009
-
负责人:Robert W McCarley
-
依托单位:
MRI Anatomy of Schizophrenia
-
批准号:8390426
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2009
-
负责人:Robert W McCarley
-
依托单位:
CLINICAL STATUS AND BRAIN FUNCTIONING IN ADOLESCENTS AND ADULTS
-
批准号:7718948
-
项目类别:
-
资助金额:$0.09万
-
财政年份:2008
-
负责人:Robert W McCarley
-
依托单位:
Vulnerability to Progression Schizophrenia
-
批准号:8136034
-
项目类别:
-
资助金额:$183.86万
-
财政年份:2007
-
负责人:Robert W McCarley
-
依托单位:
Vulnerability to Progression Schizophrenia
-
批准号:7920849
-
项目类别:
-
资助金额:$191.29万
-
财政年份:2007
-
负责人:Robert W McCarley
-
依托单位:
Vulnerability to Progression Schizophrenia
-
批准号:7498415
-
项目类别:
-
资助金额:$194.2万
-
财政年份:2007
-
负责人:Robert W McCarley
-
依托单位:
CORE 1: OPERATIONS AND CLINICAL ASSESSMENT
-
批准号:7279685
-
项目类别:
-
资助金额:$10.79万
-
财政年份:2007
-
负责人:Robert W McCarley
-
依托单位:
Vulnerability to Progression Schizophrenia
-
批准号:7684159
-
项目类别:
-
资助金额:$194.2万
-
财政年份:2007
-
负责人:Robert W McCarley
-
依托单位:
海外基金