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The Role of Medial Prefrontal Cortex in the Memory for Sequences of Events

内侧前额叶皮层在事件序列记忆中的作用

基本信息

批准号：
10348721
负责人：
Maanasa Jayachandran
金额：
$ 3.89万
依托单位：
FLORIDA INTERNATIONAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10348721
关键词：
Adaptive Behaviors Alzheimer&apos s Disease Anatomy Attention deficit hyperactivity disorder Award Back Behavior Behavioral Cells Cognition Cognitive Critical Pathways Development Disease model Electrophysiology (science)Episodic memory Event Feedback Florida Foundations Functional disorder Future Genetic Genetic Models Goals Hippocampus (Brain)Impairment Implant Information Retrieval International Investigation Knowledge Learning Medial Memory Mental disorders Mentors Methodology Mission Modeling Neurobiology Neurons Odors Pathway interactions Pattern Phase Population Positioning Attribute Postdoctoral Fellow Prefrontal Cortex Presynaptic Terminals Process Property Public Health Rattus Research Research Personnel Research Project Grants Retrieval Reuniens Thalamic Nucleus Rhodopsin Rodent Rodent Model Role Route Schizophrenia Short-Term Memory Silicon Site Stimulus Synapses Techniques Testing Thalamic structure Therapeutic Tracer Training Translational Research Underrepresented Students United States National Institutes of Health Universities Viral Work base career cell cortex cognitive neuroscience density designer receptors exclusively activated by designer drugs experimental study graduate student in vivo innovation knowledge base memory retrieval neural circuit neural correlate neural patterning neurobiological mechanism neuromechanism optogenetics programs relating to nervous system skills symposium

项目摘要

PROJECT SUMMARY/ABSTRACT Temporal organization is critical to many perceptual, cognitive, and behavioral functions. These temporal abilities are adversely impacted in several mental health disorders such as schizophrenia and attention-deficit hyperactivity disorder (ADHD). However, the neurobiological underpinnings of the temporal organization of memory and behavior remain poorly understood. Here, we will focus on specific circuits of the medial prefrontal cortex (mPFC). mPFC is positioned to influence sequence memory through extensive top-down inputs to regions heavily interconnected with the hippocampus (HC), notably the nucleus reuniens of the thalamus (RE) and perirhinal cortex (PER). We hypothesize that these different mPFC projection pathways, and their associated mPFC neuron populations differentially contribute to short- and long-term aspects of the retrieval of memory for sequences of events. We will use a sophisticated behavioral strategy testing sequence memory in rats with probes that differentially depend on working memory and temporal context memory using repeats (e.g., ABAD) and skips (e.g., ABDD) across three aims: AIM1 tests the causal roles of mPFC projections using virally-delivered inhibitory designer receptors exclusively activated by designer drugs (DREADDs; AAV- hM4Di). AIM2 examines the neural correlates (single-units, ensembles, and local field potentials) of mPFC and HC during memory for sequences of events. Additionally, we will use antidromic optogenetic stimulation (AAV- hChR2) to separate mPFC neurons based on their long-range projection targets innervating RE and PER. AIM3 extends Ms. Jayachandran's training as a post-doctoral researcher by further investigating the vulnerability of these mPFC pathways in genetic rodent models related to mental health disorders such as schizophrenia and Alzheimer's disease. These experiments will establish foundational knowledge about two specific mPFC pathways critical to memory and behavior, which will aid the development of future therapeutic strategies. Completion of the F99 phase will set a strong technical and professional foundation for the postdoctoral (K00) phase of this award. Specifically, Ms. Jayachandran will gather the skills and techniques such as high-density electrophysiological recordings, optogenetics, and professional development (e.g., attending conferences) in order to transition to the postdoctoral phase and allow progress toward the long-term goal of becoming an independent investigator.

项目总结/摘要时间组织对许多感知、认知和行为功能至关重要。这些时间在精神分裂症和注意力缺陷等几种精神疾病中，多动症（ADHD）。然而，神经生物学基础的时间组织，记忆和行为仍然知之甚少。在这里，我们将重点关注内侧前额叶的特定回路，皮质（mPFC）。mPFC的定位是通过广泛的自上而下的输入来影响序列记忆，与海马（HC）密切相关的区域，特别是丘脑的核团（RE）和嗅周皮质（perirhinal cortex，PER）。我们假设，这些不同的mPFC投射途径，以及它们的相关的mPFC神经元群体对提取的短期和长期方面有不同的贡献事件序列的存储器。我们将使用一种复杂的行为策略测试序列记忆，使用重复序列对工作记忆和时间背景记忆有差异依赖的探针大鼠 (e.g., ABAD）和跳过（例如，ABDD）的三个目标：AIM 1测试了mPFC预测的因果作用，病毒递送的抑制性设计者受体仅由设计者药物激活（DREADD; AAV- hM4Di）。AIM 2检查mPFC的神经相关性（单个单位、集合和局部场电位）， HC在事件序列的存储期间。此外，我们将使用逆向光遗传学刺激（AAV-100）。 hChR 2）来基于它们的支配RE和PER的长程投射靶分离mPFC神经元。 AIM 3通过进一步调查，扩展了Jayachandran女士作为博士后研究员的培训。这些mPFC途径在与精神健康障碍相关的遗传啮齿动物模型中的脆弱性，精神分裂症和老年痴呆症这些实验将建立两个基础知识特定的mPFC通路对记忆和行为至关重要，这将有助于未来治疗药物的开发。战略布局F99阶段的完成将为博士后（K 00）阶段。具体来说，贾亚钱德兰女士将收集技能和技术，例如高密度电生理记录、光遗传学和专业发展（例如，参加会议），以便过渡到博士后阶段，并允许向长期发展目标是成为一名独立调查员。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nucleus reuniens transiently synchronizes memory networks at beta frequencies.

DOI：
10.1038/s41467-023-40044-z
发表时间：
2023-07-19
期刊：
Nature communications
影响因子：
16.6
作者：
Jayachandran M;Viena TD;Garcia A;Veliz AV;Leyva S;Roldan V;Vertes RP;Allen TA
通讯作者：
Allen TA

Sex and estrous cycle in memory for sequences of events in rats.