Thalamic and cortical mechanisms of anesthetic-induced unconsciousness
麻醉引起无意识的丘脑和皮质机制
基本信息
- 批准号:8804277
- 负责人:
- 金额:$ 29.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-02-15 至 2017-12-31
- 项目状态:已结题
- 来源:
- 关键词:Adverse effectsAnesthesia proceduresAnestheticsAreaAuditoryAuditory areaAwarenessBiological AssayBrain StemCell NucleusCellsClinicalCodeConsciousCortical ColumnDataDevelopmentDexmedetomidineDiagnosticDoseElectrodesGeneral anesthetic drugsHealthImplantIpsilateralIsofluraneLinkMeasuresMidbrain structureMinimally Conscious StatesModalityModelingMolecularMonitorOperating RoomsOutputPathway interactionsPatient CarePatientsPopulationProcessPropofolPublic HealthRattusRecoveryScienceSensorySourceStimulusSurfaceSynapsesTechniquesTestingThalamic structureUnconscious StateVisualVisual Cortexauditory stimulusawakebasecausal modeldensitydrug developmentextrastriate visual cortexhypnoticinsightmicrostimulationpreventrelating to nervous systemresearch studyresponsesegregationsensory inputsensory stimulustheoriestoolvisual stimulus
项目摘要
DESCRIPTION (provided by applicant): Elucidating the mechanism by which anesthetics cause loss of consciousness (LOC) will benefit patient care and provide insight into the neural basis of consciousness. In this proposal, we will test two competing hypotheses, the thalamic switch hypothesis (TSH) and the information integration theory of consciousness (IITC). In the former, disruption of thalamo-cortical information transfer is thought critical for LOC. The latter
proposes that anesthetics act across wide areas of cortex to reduce the repertoire of network states (information) and connectivity (integration). We postulate that propofol, isoflurane and dexmedetomidine, acting at diverse molecular loci, share a common cortical mechanism for producing LOC: degradation of stimulus representation and suppression of cortico-cortical connectivity at just-hypnotic doses (i.e. those just causing LOC), which prevent incorporation of sensory information into cortical hierarchical processing. We will test these competing hypotheses by recording unit activity and local field potentials (LFPs) in rats chronically implanted with multisite electrodes in auditory thalamus and auditory and visual cortex. A practical benefit to public health will be assays of consciousness based on population codes and cortical connectivity derived from cortical surface recordings, which are readily obtained in clinical settings. The absence of sensory awareness is a manifestation of LOC that reflects degraded information transfer between the periphery and high order cortex, but where and how this breakdown occurs is unclear. In the first Aim, we will focus on how much information responses of cells in auditory cortex carry about sensory stimuli, both at the single cell level an at the population level, and how this information changes upon loss and recovery of consciousness (LOC/ROC). By recording auditory responses in two thalamic areas, MGv and MGd, and their respective hierarchically connected cortical targets, A1 and PAF, we can determine whether anesthetics block information transfer from thalamus to cortex, as predicted by the TSH, or whether even in the face of maintained thalamic input cortical responses become impoverished upon LOC due to observed changes in local network activity caused by anesthetics, consistent with the IITC. In the second and third Aims, we will investigate connectivity along the ascending and descending thalamo-cortical pathway. Here we will record synaptic and spiking activity in entire cortical columns in response to microstimulation and auditory and visual sensory stimuli to determine if connectivity changes upon LOC/ROC at thalamo-cortical synapses, as predicted by the TSH, or at cortico-cortical synapses, consistent with the IITC. We will use the information from these experiments to aid in seeking electrophysiological correlates of the state transitions manifested in LOC/ROC, and we will derive clinically accessible measures of sensory awareness based on population coding and cortical connectivity using state of the art analysis and modeling techniques.
描述(由申请人提供):阐明麻醉剂导致意识丧失(意识丧失)的机制将有利于患者护理,并提供对意识神经基础的深入了解。在这个建议中,我们将测试两个相互竞争的假设,丘脑开关假说(TSH)和意识的信息整合理论(IITC)。在前一种情况下,丘脑-皮层信息传递的中断被认为是神经衰弱的关键。后者
提出,麻醉剂作用于大脑皮层的广泛区域,以减少网络状态(信息)和连接(整合)的库。我们假设异丙酚、异氟烷和右美托咪定作用于不同的分子位点,具有共同的皮质机制来产生催眠:在催眠剂量下(即仅引起催眠的剂量),刺激表征的降解和皮质-皮质连接的抑制,这阻止了感觉信息并入皮质分层处理。我们将测试这些竞争的假设,记录单位活动和局部场电位(LFPs)在大鼠长期植入多点电极在听觉丘脑和听觉和视觉皮层。对公共卫生的实际益处将是基于群体代码和来自皮层表面记录的皮层连接的意识测定,这在临床环境中很容易获得。 感觉意识的缺失是一种神经衰弱的表现,反映了外围和高级皮层之间的信息传递退化,但这种故障在哪里以及如何发生尚不清楚。在第一个目标中,我们将专注于听觉皮层细胞对感觉刺激的信息反应,无论是在单细胞水平还是在群体水平,以及这些信息在意识丧失和恢复(ROC/ROC)时如何变化。通过记录两个丘脑区域MGv和MGd以及它们各自的分层连接的皮层靶区A1和PAF中的听觉反应,我们可以确定麻醉剂是否会阻止信息从丘脑传递到皮层,正如TSH所预测的那样,或者即使在维持丘脑输入的情况下,由于观察到的麻醉剂引起的局部网络活动的变化,与IITC一致。在第二个和第三个目标中,我们将研究沿着上行和下行丘脑-皮质通路的连接性。在这里,我们将记录突触和尖峰活动,在整个皮质列响应微刺激和听觉和视觉感官刺激,以确定是否连接性变化后,在丘脑-皮质突触,如TSH预测的,或在皮质-皮质突触,与IITC一致的ROC/ROC。我们将使用这些实验的信息,以帮助寻求电生理学相关的状态转换表现在ROC/ROC,我们将获得临床上可访问的措施的感觉意识的基础上,人口编码和皮质连接使用最先进的分析和建模技术。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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Matthew I Banks其他文献
Matthew I Banks的其他文献
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{{ truncateString('Matthew I Banks', 18)}}的其他基金
Mechanisms of Loss, Recovery and Disorders of Consciousness
意识丧失、恢复和障碍的机制
- 批准号:
10607642 - 财政年份:2014
- 资助金额:
$ 29.76万 - 项目类别:
Mechanisms of anesthetic-induced unconsciousness
麻醉引起的意识丧失的机制
- 批准号:
10387932 - 财政年份:2014
- 资助金额:
$ 29.76万 - 项目类别:
Mechanisms of anesthetic-induced unconsciousness
麻醉引起的意识丧失的机制
- 批准号:
9750291 - 财政年份:2014
- 资助金额:
$ 29.76万 - 项目类别:
Mechanisms of anesthetic-induced unconsciousness
麻醉引起的意识丧失的机制
- 批准号:
10162613 - 财政年份:2014
- 资助金额:
$ 29.76万 - 项目类别:
Thalamic and cortical mechanisms of anesthetic-induced unconsciousness
麻醉引起无意识的丘脑和皮质机制
- 批准号:
8990491 - 财政年份:2014
- 资助金额:
$ 29.76万 - 项目类别:
Thalamic and cortical mechanisms of anesthetic-induced unconsciousness
麻醉引起无意识的丘脑和皮质机制
- 批准号:
8615727 - 财政年份:2014
- 资助金额:
$ 29.76万 - 项目类别:
Thalamic and cortical mechanisms of anesthetic-induced unconsciousness
麻醉引起无意识的丘脑和皮质机制
- 批准号:
9189624 - 财政年份:2014
- 资助金额:
$ 29.76万 - 项目类别:
Integration of ascending and descending input to auditory cortex
整合听觉皮层的上升和下降输入
- 批准号:
7893247 - 财政年份:2003
- 资助金额:
$ 29.76万 - 项目类别: