Understanding neural circuits for associative memory in the lateral entorhinal cortex

了解外侧内嗅皮层联想记忆的神经回路

• 批准号: 10659182
• 负责人: Kei M Igarashi
• 金额: $ 39.39万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-12 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10659182
• 关键词: Acceleration; Address; Affect; Alzheimer' s Disease; Anatomy; Animals; Area; Association Learning; Brain; Cells; Cues; Data; Dementia; Dimensions; Dopamine; Dopamine Antagonists; Electrophysiology (science); Environment; Etiology; Exhibits; Fiber; Generations; Goals; Hippocampus; Homologous Gene; Impairment; Individual; Injections; Interneurons; Knowledge; Label; Lateral; Learning; Medial; Memory; Memory impairment; Methods; Mind; Mus; Neurons; Odors; Outcome; Parvalbumins; Pathogenesis; Performance; Persons; Photometry; Play; Positioning Attribute; Presynaptic Terminals; Proteins; Public Health; Rattus; Research; Retrieval; Rewards; Role; Sensory; Signal Transduction; Testing; Transgenic Mice; Type II Epithelial Receptor Cell; United States; Wolfram Syndrome; analytical method; cell type; design; dopamine system; dopamine transporter; entorhinal cortex; experimental study; in vivo; memory retrieval; neural circuit; neuronal circuitry; optical imaging; optogenetics; pharmacologic; promoter; recruit; segregation; spatial memory; way finding; Acceleration; Address; Affect; Alzheimer' s Disease; Anatomy; Animals; Area; Association Learning; Brain; Cells; Cues; Data; Dementia; Dimensions; Dopamine; Dopamine Antagonists; Electrophysiology (science); Environment; Etiology; Exhibits; Fiber; Generations; Goals; Hippocampus; Homologous Gene; Impairment; Individual; Injections; Interneurons; Knowledge; Label; Lateral; Learning; Medial; Memory; Memory impairment; Methods; Mind; Mus; Neurons; Odors; Outcome; Parvalbumins; Pathogenesis; Performance; Persons; Photometry; Play; Positioning Attribute; Presynaptic Terminals; Proteins; Public Health; Rattus; Research; Retrieval; Rewards; Role; Sensory; Signal Transduction; Testing; Transgenic Mice; Type II Epithelial Receptor Cell; United States; Wolfram Syndrome; analytical method; cell type; design; dopamine system; dopamine transporter; entorhinal cortex; experimental study; in vivo; memory retrieval; neural circuit; neuronal circuitry; optical imaging; optogenetics; pharmacologic; promoter; recruit; segregation; spatial memory; way finding

Abstract The entorhinal cortex (EC) and the hippocampus are the brain areas which are critically involved in the formation and retrieval of declarative memory, and damage to this circuit results in memory impairment. In order to cure dementias, including Alzheimer’s disease, which currently affects 5 million people in the United States, it is critical to forward an understanding of the cellular and circuit mechanisms involved in the encoding and retrieval of memory in this entorhinal-hippocampal circuit. The EC is anatomically segregated into two halves, the lateral entorhinal cortex (LEC), and the medial entorhinal cortex (MEC). Although previous studies have significantly advanced our understanding of the functional role of the MEC in spatial memory and navigation, our understanding of the functions of the LEC remain largely unclear. Here we propose studies to investigate the function of the LEC in the associative memory to address this critical gap in knowledge. Our approach involves multi-faceted analytical methods including in vivo electrophysiology, associative learning tasks, optogenetic circuit analysis methods, optical imaging and transgenic mouse lines that express Cre mice under the promoter of cell-type-specific markers. There are three Specific Aims to the studies: (Aim 1) identify functional roles of LEC layer II cell types in associative learning; (Aim 2) identify the role of LEC dopamine input in associative learning; and (Aim 3) determine the causal role of LEC 20-40Hz oscillations in associative learning. If successful, our studies will identify the circuit mechanisms for associative memory formation in the LEC and will help establish new frameworks for understanding how the entorhinal-hippocampal circuit enables the formation of declarative memory via the integration of multiple dimensions of sensory information.

抽象的 内嗅皮层（EC）和海马是大脑区域，与地层非常重要 并检索声明性记忆和对该电路的损坏会导致记忆力障碍。为了治愈 痴呆症，包括目前影响美国500万人的阿尔茨海默氏病，这是至关重要的 要转发对编码和检索涉及的细胞和电路机制的理解 在此内嗅 - 海马电路中的记忆。 EC在解剖学上分为两半，后来 内嗅皮层（LEC）和中位内嗅皮层（MEC）。尽管以前的研究显着 提高了我们对MEC在空间内存和导航中的功能作用的理解，我们 对LEC功能的理解在很大程度上不清楚。在这里，我们建议研究 LEC在关联内存中的功能，以解决知识中的这一关键差距。我们的方法涉及 多面分析方法，包括体内电生理学，关联学习任务，光遗传学 电路分析方法，光学成像和转基因小鼠线，在启动子下表达CRE小鼠 细胞型特异性标记。研究有三个具体目的：（目标1）确定功能角色 联想学习中的LEC II层细胞类型； （AIM 2）确定LEC多巴胺输入在联想中的作用 学习; （目标3）确定LEC 20-40Hz振荡在关联学习中的因果作用。如果成功， 我们的研究将确定LEC中关联记忆形成的电路机制，并将有助于 建立新的框架，以了解肠hin鼻 - 海马电路如何形成 通过集成感官信息的多个维度来声明记忆。