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.

与许多静脉注射药物不同，吸入麻醉剂通过调节多个靶点来达到其作用