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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.

项目摘要/摘要时间组织对许多感知、认知和行为功能至关重要。这些时间精神分裂症和注意力缺陷等几种精神健康障碍会对能力产生不利影响多动症(ADHD)。然而，时间组织的神经生物学基础记忆和行为仍然知之甚少。在这里，我们将集中在内侧前额叶的特定环路皮质(MPFC)。MPFC的定位是通过广泛的自上而下输入来影响序列记忆与海马体(HC)紧密相连的区域，特别是丘脑(RE)的团状核和口周皮质(PER)。我们假设这些不同的mPFC投射路径，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顺序的存储器。我们将使用复杂的行为策略测试序列记忆大鼠的探测不同地依赖于工作记忆和使用重复的时间背景记忆 (例如，ABAD)和跳过(例如，ABDD)三个目标：AIM1测试mPFC预测的因果作用，使用病毒递送的抑制性设计受体，由设计药物(DREADDS；AAV- HM4Di)。AIM2检查mPFC和mPFC的神经关联(单个单位、集合和局部场电位) 在用于事件序列的记忆期间的HC。此外，我们将使用逆行光遗传刺激(AAV- HChR2)根据其支配RE和PER的远程投射靶点来分离mPFC神经元。 AIM3通过进一步调查Jayachandran女士作为博士后研究员的这些mPFC通路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阿尔茨海默病。这些实验将建立关于两个方面的基础知识特定的mPFC通路对记忆和行为至关重要，这将有助于未来治疗的发展战略。F99阶段的完成将为以下工作奠定坚实的技术和专业基础该奖项的博士后(K00)阶段。具体地说，贾亚昌德兰将收集技能和技巧例如高密度电生理记录、光遗传学和职业发展(例如，参加会议)，以便过渡到博士后阶段，并使长期成为一名独立调查员的目标。

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.