Synaptic and Circuit Interactions to Shape Multisensory Processing

突触和电路相互作用塑造多感官处理

• 批准号: 9769910
• 负责人: Jayeeta Basu
• 金额: $ 37.97万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769910
• 关键词: Affect; Alzheimer' s Disease; Anatomy; Area; Association Learning; Axon; Back; Behavior; Behavioral; Brain; Cells; Communication; Cues; Dendrites; Detection; Electrophysiology (science); Emotional; Exercise; Feedback; Functional disorder; Head; Hippocampus (Brain); Impaired cognition; In Vitro; Lateral; Learning; Long-Term Potentiation; Medial; Memory; Modeling; Mus; Names; Neurologic; Neurons; Neurosciences; Output; Pathway interactions; Patients; Pattern; Performance; Phase; Play; Post-Traumatic Stress Disorders; Process; Property; Research; Role; Route; Sampling; Schizophrenia; Sensory; Shapes; Signal Transduction; Symptoms; Synapses; Synaptic Transmission; Testing; Time; Viral; autism spectrum disorder; base; behavior test; behavioral impairment; entorhinal cortex; environmental change; experience; experimental study; improved; in vivo; information processing; insight; learned behavior; light gated; long term memory; loss of function; memory process; multisensory; nervous system disorder; neural circuit; neuromechanism; neuropsychiatric disorder; neuropsychiatry; novel; optogenetics; parallel processing; relating to nervous system; response; sensory cortex; sensory gating; sensory input; time interval

A critical step during sensory processing is the extraction of relevant information about the outside world from a host of distracting sensory inputs. One mechanism for generating salience is to associate sensory information from ongoing experiences with memories derived from past sensory experiences. Where and how these functional associations occur in the brain are central questions in neuroscience. This proposal aims to fill this gap by exploring circuit interactions and single neuron computations that help assign mnemonic valence to sensory signals. In this study, we propose that the hippocampus—the center of learning and memory—plays a crucial role in gating sensory information flow through its reciprocal circuit interactions with the entorhinal cortex, a hub for processing multisensory information. To test this hypothesis, we will use anatomical and functional connectivity mapping experiments to validate how hippocampus communicates with entorhinal cortex output layers (Aim 1). We will assess how hippocampal inputs modulate the short-term plasticity dynamics of excitatory-inhibitory synaptic transmission in the entorhinal cortex (Aim 2). Finally, we will test whether the hippocampus actively modulates the synaptic strength and gain of sensory inputs to entorhinal cortex through dendritic integration and long-term plasticity mechanisms (Aim 3a) and how silencing the CA1 inputs to EC will affect contextual learning behavior (Aim 3b). Despite 60 years of research on memory processing, we know surprisingly little about the organization and function of hippocampal projection circuitry and the mechanisms by which memories modulate ongoing sensory processing in the entorhinal cortex. Our study will combine state-of-the-art in vitro and in vivo approaches, including electrophysiology, behavioral testing, and optogenetics, to provide a functional model of the unexplored hippocampal-entorhinal cortex reciprocal circuit. Exciting pilot experiments from our lab have already revealed a new pathway between the hippocampus and entorhinal cortex that implies a true reciprocal feedback circuit loop. This circuit connects the hippocampus directly to entorhinal cortex output neurons that project sensory information to the hippocampus. Our new circuit model is potentially transformative, for it describes a route by which the hippocampus directly transmits memory input to the entorhinal cortex, with minimal lag and transformation, to refine sensory output based on relevance and to quickly adapt behavior in response to changing environmental demands. Such a function could be used by the brain to facilitate reinforced learning, refine old memories, and form new memory associations. By identifying the neural circuit interactions between the hippocampus and entorhinal cortex, our study will greatly improve our understanding of the mechanisms that underlie the memory-related sensory processing deficits experienced by patients of several neurological and neuropsychiatric illnesses, including Alzheimer’s disease, schizophrenia and PTSD.

感觉加工过程中的一个关键步骤是从一个人的大脑中提取关于外部世界的相关信息。 大量分散注意力的感官输入产生显著性的一种机制是将感官信息 从过去的感官体验中获得的记忆。在哪里以及如何这些 大脑中发生的功能性关联是神经科学的中心问题。该提案旨在填补这一 通过探索电路相互作用和单个神经元计算来帮助分配助记符， 感知信号的效价。在这项研究中，我们提出，大学校园-学习的中心， 记忆-在门控感官信息流通过其互惠电路相互作用， 内嗅皮层是处理多感官信息的中枢。为了验证这个假设，我们将使用 解剖和功能连接映射实验，以验证海马体如何与 内嗅皮层输出层（Aim 1）。我们将评估海马输入如何调节短期 内嗅皮层兴奋-抑制性突触传递的可塑性动力学（目的2）。最后我们 将测试海马体是否主动调节突触强度和感觉输入的增益， 内嗅皮层通过树突整合和长期可塑性机制（目的3a）以及如何沉默 对EC的CA 1输入会影响情境学习行为（目标3b）。 尽管对记忆处理的研究已经有60年了，但我们对记忆的组织却知之甚少， 海马投射回路的功能以及记忆调节持续进行的 内嗅皮层的感觉处理我们的研究将联合收割机最新的体外和体内研究相结合 方法，包括电生理学，行为测试和光遗传学，以提供一个功能模型， 尚未探索的大脑皮层-内嗅皮层相互回路我们实验室令人兴奋的试点实验 已经揭示了海马体和内嗅皮层之间的一条新通路，这意味着真正的互惠关系。 反馈回路这个回路将海马体直接连接到内嗅皮层输出神经元， 将感觉信息投射到海马体。我们的新电路模型具有潜在的变革性， 描述了海马体直接将记忆输入传递到内嗅皮层的途径， 最小的滞后和转换，以完善基于相关性的感官输出，并快速适应 应对不断变化的环境需求。这样的功能可以被大脑用来促进 强化学习，提炼旧的记忆，形成新的记忆联想。通过识别神经回路 海马和内嗅皮层之间的相互作用，我们的研究将大大提高我们的理解 的机制，其基础的记忆相关的感觉处理缺陷的患者所经历的 几种神经和神经精神疾病，包括阿尔茨海默病，精神分裂症和创伤后应激障碍。