Prospective Coding and Memory Retrieval

前瞻性编码和记忆检索

• 批准号: 9904758
• 负责人: Matthew L Shapiro
• 金额: $ 34.72万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904758
• 关键词: Affect; Area; Axon; Basal Nucleus of Meynert; Behavior; Behavioral; Bilateral; Brain; Cannulas; Code; Cognitive; Communication; Data; Discrimination; Electrodes; Episodic memory; Fimbria of hippocampus; Functional disorder; Goals; Halorhodopsins; Hippocampus (Brain); Impairment; Implant; Infusion procedures; Learning; Light; Link; Location; Medial; Memory; Mental Depression; Mental disorders; Muscimol; Names; Neurons; Neuropsychology; Operative Surgical Procedures; Outcome; Output; Pacemakers; Pattern; Performance; Phase; Physiological; Population; Prefrontal Cortex; Presynaptic Terminals; Rattus; Recording of previous events; Reuniens Thalamic Nucleus; Reversal Learning; Rewards; Role; Schizophrenia; Septal Area; Septal Nuclei; Series; Space Perception; Specific qualifier value; Stimulus; Structure; Temporal Lobe; Testing; Thalamic structure; Time; Training; Virus; autism spectrum disorder; base; density; design; expectation; experience; experimental study; flexibility; improved; memory retrieval; network architecture; neuromechanism; neurotransmission; optical fiber; outcome prediction; predictive signature; prospective; relating to nervous system; severe psychiatric disorder; transmission process; vector

Memory evolved to predict outcomes, but the neural mechanisms that link outcomes and remembered episodes are unclear. Episodic memory requires the hippocampus (HPC), working flexibly with memory requires the prefrontal cortex (PFC), and both structures are needed for tracking outcomes that change over space or time. Spatial reversal learning entails learning to stop approaching a previously rewarded location and instead approaching a previously unrewarded one. The PFC and HPC are needed for spatial reversal learning, and each structure supports different functions. HPC inactivation impairs all spatial learning, whereas PFC inactivation spares discrimination but impair reversal learning. Different PFC circuits guide reversals depending on outcome history: medial prefrontal cortex (mPFC) supports switching between rapidly changing goals, orbitofrontal cortex (OFC) supports switching from one well-established goal to another. Neural representations in each structure predict choices that correspond with the inactivation effects: OFC predictions develop relatively slowly across episodes, while mPFC and HPC predictions develop quickly. The proposed experiments combine local circuit manipulations with high density unit recording in rats performing spatial reversals to test the extent to which coordinated HPC and PFC activity associates episodes and outcomes. Aim 1 will test how outcome history affects reversal strategies and functional interactions between PFC and CA1 by disrupting local circuits. Groups of rats will be trained in a HPC-dependent spatial task followed by reversals designed to require either OFC or mPFC while local OFC or mPFC circuits are temporarily inactivated. To investigate the required circuitry, mPFC and OFC will be infected with halorhodopsin (NpHR3.0) or channelrhodopsin (ChR2) containing viruses and PFC axon terminals will be modulated by light delivered to the n. reuniens, a thalamic relay between PFC and CA1. The results will determine if mPFC and OFC contribute independently or interactively to spatial outcome predictions, and test the extent to which these interactions require the n. reuniens. Aim 2 will investigate how outcome history affects PFC and CA1 coding interactions by recording simultaneously in the three regions or inactivating one while recording the other two as rats perform the tasks described in Aim 1. The results will identify neuronal signals and CA1 interactions with mPFC or OFC that predict outcome guided memory representations. Aim 3 will test PFC-HPC communication mechanisms by modulating the temporal coordination of PFC and HPC activity. Electrically stimulating the fimbria fornix synchronizes local field potentials in widespread cortical and subcortical networks and improves spatial learning and memory. “Pacemaker” stimulation of the medial septal area (MSA) and nucleus basalis modulate HPC and PFC synchrony independently. Enhancing or disrupting learning-related activity patterns recorded in Aim 2 will test if network synchrony is needed to link outcomes with memory.

记忆的进化是为了预测结果，但是将结果和记忆联系起来的神经机制 情节尚不清楚。情节记忆需要海马体（HPC），灵活地与记忆一起工作 需要前额叶皮层（PFC），这两个结构都需要跟踪变化的结果， 空间或时间。空间逆转学习需要学习停止接近之前奖励的位置， 而不是接近一个以前没有得到回报的人。PFC和HPC是空间反向学习所必需的， 并且每个结构支持不同的功能。HPC失活损害所有空间学习，而PFC 失活避免了辨别，但损害了反向学习。不同的PFC电路引导反转， 关于结果历史：内侧前额叶皮层（mPFC）支持在快速变化的目标之间切换， 眶额皮质（OFC）支持从一个既定目标切换到另一个目标。神经表征 在每个结构中，预测与失活效应相对应的选择：OFC预测发展 在不同的事件中，mPFC和HPC的预测相对较慢，而mPFC和HPC的预测发展迅速。拟议 实验联合收割机局部电路操作与高密度单位记录在大鼠进行空间 逆转，以测试协调HPC和PFC活动关联事件和结果的程度。 目标1将测试结果历史如何影响逆转策略以及PFC和 CA 1通过破坏本地电路。将在HPC依赖性空间任务中训练大鼠组，然后 当局部OFC或mPFC电路暂时 灭活为了研究所需的电路，mPFC和OFC将被盐视紫红质感染 含有病毒和PFC轴突末端的NpHR3.0或ChR 2通道视紫红质（ChR 2）将被光调制 送到，送到reuniens，PFC和CA 1之间的丘脑中继。结果将确定mPFC和 OFC独立或交互地对空间结果预测做出贡献，并测试这些预测的程度。 相互作用需要N。团聚。目标2将研究结局史如何影响PFC和CA 1编码 通过在三个区域中同时记录或在记录其他两个区域的同时使一个区域失活， 当大鼠执行目标1中描述的任务时。结果将确定神经元信号和CA 1相互作用 mPFC或OFC来预测结果引导的记忆表征。目标3将测试PFC-HPC 通信机制通过调节PFC和HPC活动的时间协调。电 刺激穹窿海马伞在广泛的皮层和皮层下网络中的局部场电位 并改善空间学习和记忆。内侧隔区（MSA）的“起搏器”刺激， 基底核独立调节HPC和PFC的同步性。加强或破坏与学习有关的 目标2中记录的活动模式将测试是否需要网络同步来将结果与记忆联系起来。