Anesthetics & cerebral cortical sensory integration

麻醉剂

• 批准号: 6687447
• 负责人: Anthony George Hudetz
• 金额: $ 31.5万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6687447
• 关键词: brain electrical activity; chemical stimulation; consciousness; halothane; isoflurane; laboratory rat; neuropharmacology; neurotensin; neurotransmitters; reflex; respiratory oxygenation; sensory depression; visual cortex; visual stimulus

DESCRIPTION (provided by applicant): The overall goal of our research is to better understand the mechanism of general anesthesia at an integrative level with special reference to the toss and return of conscious sensory functions. The general hypothesis is that a neural correlate of volatile anesthetic-induced loss of consciousness (LOC) is the disruption of gamma-frequency synchronization of neuronal activity among primary sensory and association cortices. This work focuses onthe anesthetic modulation of visual cortical function in the rat and applies a combination of intracortical field potential (FP) and multichannel unit activity (UA) recordings and functional magnetic resonance imaging (fMRI) to determine the respective effects of halothane and isoflurane. The loss of righting reflex (LORR) will be used as a behavioral index of LOC assessed simultaneously with the electrophysiological recordings in freely moving rats. Four specific hypotheses that we will test are: (1) synchronization of visual stimulus-induced FP gamma oscillations among specific visual and fronto-parietal association cortical regions is diminished by both agents at concentrations corresponding to LORR; (2) UA of neuronal populations will follow the FP gamma oscillations such that the visual stimulus-related neuronal firing synchrony among cortical regions will be diminished with increasing anesthetic concentration in correlation with the LORR; (3) anesthetic depression of poststimulus cortico-cortical gamma synchronization and the righting reflex will both be restored by cortical arousal achieved by electrical or pharmacological (glutamate, norepinephrine, neurotensin) stimulation of the basal forebrain (n. basalis of Meynert) or the parabrachial region (n. cuneiformis); (4) cortical blood oxygen level dependent (BOLD) fMRI response to visual stimulation will correlate with the gamma FP response and J will be reduced in parallel with cortico-cortical functional connectivity at increasing depth of anesthesia. Analysis of functional connectivity will involve the determination of synchrony and mutual information of FP and UA recorded with chronically implanted bipolar electrodes and high density microelectrode arraysl sampling simultaneously more than 100 neurons. This research should advance our understanding of the neurobiological basis of consciousness and the mechanism of sedative/hypnotic effect of general anesthetic agents and may lead to the development of more specific agents and of monitors of anesthetic depth monitors.

描述（由申请人提供）： 我们研究的总体目标是更好地了解全身麻醉的机制，特别是在整体水平上的意识感觉功能的折腾和恢复。一般的假设是，挥发性麻醉剂引起的意识丧失（VEP）的神经相关性是初级感觉和联合皮层之间神经元活动的γ频率同步的破坏。本研究的重点是麻醉剂对大鼠视皮层功能的调节，并结合皮层内场电位（FP）和多通道单位活动（UA）记录和功能磁共振成像（fMRI）来确定氟烷和异氟烷各自的作用。翻正反射丧失（LORR）将用作与自由活动大鼠的电生理记录同时评估的翻正反射的行为指标。我们将检验的四个具体假设是：（1）在对应于LORR的浓度下，两种药物都减弱了特定视觉和额顶叶联合皮层区域中视觉刺激诱导的FP γ振荡的同步性;（2）神经元群的UA将跟随FP γ振荡，使得视觉刺激-皮质区域之间的相关神经元放电同步性将随着与LORR相关的麻醉剂浓度的增加而减弱;（3）刺激后皮层-皮层γ同步化和翻正反射的麻醉抑制都将通过电或药物刺激实现的皮层唤醒而恢复。（谷氨酸、去甲肾上腺素、神经降压素）刺激基底前脑（n. Meynert的basalis）或臂旁区（n.楔状肌）;（4）皮层血氧水平依赖性（BOLD）fMRI对视觉刺激的反应将与γ FP反应相关，并且随着麻醉深度的增加，J将与皮层-皮层功能连接平行地降低。功能连接性的分析将涉及确定FP和UA的同步性和互信息，所述FP和UA由长期植入的双极电极和同时采样超过100个神经元的高密度微电极阵列记录。这项研究将促进我们对意识的神经生物学基础和全身麻醉药镇静/催眠作用机制的理解，并可能导致更具体的药物和麻醉深度监测仪的开发。