Optogenetic disruption of the multi-synaptic pathway to CA1 during hippocampal oscillations

海马振荡期间 CA1 多突触通路的光遗传学破坏

• 批准号: 9068352
• 负责人: KAMRAN DIBA
• 金额: $ 18.43万
• 依托单位: UNIVERSITY OF WISCONSIN MILWAUKEE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9068352
• 关键词: Acute; Affect; Alzheimer' s Disease; Anesthesia procedures; Behavior; Behavioral; Brain; Cells; Characteristics; Chronic; Clinical; Conflict (Psychology); Data; Dementia; Disease; Environment; Epilepsy; Episodic memory; Event; Experimental Designs; Functional disorder; Health; Hippocampal Formation; Hippocampus (Brain); Influentials; Investigation; Light; Link; Measures; Mediating; Memory; Memory impairment; Neurodegenerative Disorders; Neurons; Pathway interactions; Pattern; Performance; Phase; Play; Population; Positioning Attribute; Process; Protocols documentation; Proton Pump; Published Comment; Rattus; Recurrence; Role; Schizophrenia; Shapes; Short-Term Memory; Source; Spatial Behavior; Staging; Study models; Symptoms; Synapses; Task Performances; Testing; Theoretical Studies; Urethane; Work; arm; awake; base; control trial; dentate gyrus; entorhinal cortex; hippocampal pyramidal neuron; in vivo; indexing; mossy fiber; neuropathology; neurophysiology; optogenetics; place fields; postsynaptic; preference; relating to nervous system; research study; targeted treatment; tool

 DESCRIPTION (provided by applicant): The hippocampal circuit of the brain is considered to be responsible for storage and recall of episodic memory. Within this circuit, activity propagates through at least two distinct pathways. Comprising the input to CA1 neurons, neural activity arrives either directly from layer III of the entorhinal cortex, or through a multi-synaptic chain involving the recurrently connected CA3 region. A number of important experimental and theoretical studies have targeted the role and effect of each of these pathways on neural activity observable at CA1 but, due to various limitations, have resulted in incomplete and often contradictory viewpoints. In this project, we aim to untangle the postsynaptic effect of these two input pathways to region CA1 by performing optogenetic inactivation of region CA3 pyramidal neurons in the rat hippocampus during a specific set of in vivo network states while recording large-scale neuronal activity in CA3 and CA1. Our working hypothesis is that the multi-synaptic pathway through CA3 represents a major source of input to CA1 and as such should have a significant postsynaptic effect during key phases of oscillatory activity. We will test this hypothesis in a number of specific aims to determine and characterize the effect of region CA3 on CA1 activity separately during theta, gamma, and sharp-wave ripple oscillations, in urethane-anesthetized rats (Aims 1a and 1b), during behavior in a delayed alternation task (Aim 2), and to correlate these with behavioral effects on performance in a spatial alternation task (Aim 3). The neuronal firing patterns of CA1 neurons during theta, gamma and ripple oscillations are widely considered to play critical roles in serving the mnemonic function of the hippocampus. Thus, we expect that this work will provide a major advance forward on two fronts: in our understanding of the role of the hippocampal multi-synaptic pathway and in our understanding of how the convergence of input at different phases of theta and gamma oscillations subserves the functions of the hippocampus.

 描述（由适用提供）：大脑的海马电路被认为是造成情节记忆的存储和回忆。在该电路中，活动通过至少两个不同的途径传播。包括CA1神经元的输入，神经元活性直接来自内嗅皮层的第三层，或者通过涉及经常连接的CA3区域的多突触链。许多重要的实验和理论研究已针对每种途径对可观察到的CA1神经元活性的作用和作用，但是由于各种局限性，导致了不完整且通常是矛盾的观点。在这个项目中，我们旨在通过在一组特定的体内网络态在CA3和CA1记录大型神经元活性的同时，在大鼠海马中对区域CA3锥体神经元进行光遗传学失活，从而解开这两种输入途径到CA1区域CA1的突触后效应。我们的工作假设是，通过CA3的多突触途径代表了CA1的主要输入来源，因此在振荡活性的关键阶段中应具有显着的突触后效应。我们将以许多具体的目的测试该假设，以确定和表征区域CA3对CA1在Theta，γ和锋利的波浪波动振荡期间分别在尿素 - 尿液学的大鼠中（AIMS 1A和1B）（目标1A和1B），在行为中，在延迟的替代任务中（AIM 2），以及与行为效应相关联（AIMS 1A和1B），以及将行为效果相关联（AIM 2）。在theta，伽马和波纹振荡期间，CA1神经元的神经元触发模式被广泛认为在服务海马的助攻功能方面起着关键作用。这是我们预计，这项工作将在两个方面提供一个重大的前进：在我们理解海马多突触途径的作用时，以及我们对theta和gamma振荡不同阶段输入的收敛如何在海马振荡的不同阶段的理解中。