Inhaled Anesthestic Modulation of Hippocampal Circuits

海马回路的吸入麻醉调节

• 批准号: 8473886
• 负责人: ROBERT A PEARCE
• 金额: $ 27.55万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8473886
• 关键词: Accounting; Acids; Address; Affect; Aminobutyric Acids; Amnesia; Anesthetics; Animals; Attenuated; Behavioral; Breathing; Chemosensitization; Collaborations; Complement; D Aspartate; Dose; Electrodes; Etomidate; Excitatory Synapse; Frequencies; Funding; Genetic; Hippocampus (Brain); In Vitro; Individual; Inhibitory Synapse; Intravenous; Isoflurane; Knowledge; Learning; Limes; Measures; Mediating; Memory; Modeling; Mus; Mutation; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Nature; Neurons; Pattern; Pharmaceutical Preparations; Phase; Phosphonic Acids; Process; Relative (related person); Signal Transduction; Site; Slice; Stimulus; Synapses; Synaptic plasticity; System; Testing; Time; aspartate receptor; attenuation; awake; gamma-Aminobutyric Acid; in vivo; memory encoding; mutant; prevent; receptor; response; synaptic function

Unlike many intravenous agents, inhaled anesthetics modulate multiple targets to achieve their effects. Our previous studies showed that amnestic concentrations of isoflurane substantially alter synaptic function mediated by both excitatory A/-methyl-D-aspartate receptors (NMDA-Rs) and inhil)itory v-aminobutyrlc acid type A receptors (GABAA-RS), but that neither action alone is sufficient lo account for the amnestic effect of isoflurane. We propose to study the corribined actions on these two systems, examining several integrative cellular and network processes that support synaptic plasticity and memory encoding by the hippocampus. These studies address the central hypothesis that the combinod action of inhaled anesthetics on excUatop/ and inhibitory siqnslina suppresses learning and ivdmoiv hv inloifeiiiia with dendritic integration dating the initial encoding process leading to synaptic olaslicitv. Thus, Wewill test {1) whether anesthetic tnodulation of inhibition and excitation with selective drugs (alone or in cprnbination) is antagonistic, additive, or synergistic on circuit, network, and behavioral! responses, and whether these actions in combination can account for the amnestic effect of isoflurane; (2) whether circuil-and network-level effects of isoflurane are attenuated in mice carrying genelicalterations that render specific receptors insensitive to inhaled anesthetics; and (3) whether rhythmic fluctuations in excitability dunng oscillatory network states affect the capacity of anesthetics to suppress dendritic integration arid hippocampal plasticity.

与许多静脉注射剂不同，吸入的麻醉剂调节多个靶标，以实现其 效果。我们先前的研究表明，异氟烷的浓度大大改变了 由兴奋性A/ - 甲基-D-天冬氨酸受体（NMDA-RS）和 Inhil）Itory V-氨基丁基酸A型受体（GABAA-RS），但单独的动作都足够 LO解释了异氟烷的动蛋白。我们建议研究对这些的犯错行为 两个系统，检查了支持突触的几个集成蜂窝和网络过程 海马编码的可塑性和记忆。这些研究涉及中心假设 吸入麻醉药在excuatop/ and抑制性siqnslina上的组合作用抑制 学习和ivdmoiv hv inloifieiiiia具有树突状集成约会的初始编码过程 导致突触Olaslicitv。因此，WEWILL测试{1）是否对抑制和 选择性药物的激发（单独或在c cprnbination中）是拮抗，添加剂或协同作用的 电路，网络和行为！答复以及这些组合的这些行动是否可以说明 对于异氟烷的柔滑作用； （2）异氟烷的电路和网络级效应是 在携带基因化的小鼠中减弱，使特定受体对吸入不敏感 麻醉药； （3）兴奋性振荡网络中是否有节奏的波动 影响麻醉剂抑制树突状融合的能力干旱海马可塑性。