The role of cortical long-range GABAergic inhibition on emotional learning

皮质长程 GABA 能抑制对情绪学习的作用

基本信息

  • 批准号:
    10551286
  • 负责人:
  • 金额:
    $ 59.04万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-04-10 至 2025-01-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT Proper emotional responses are characterized by the dynamic interplay of two major forces: excitation and inhibition. A current belief is that dysfunction of inhibition, mediated by local GABAergic interneurons, leads to a wide range of psychopathologies including phobias and anxiety disorders. A well-established principle of the circuit organization underlying emotional learning is that inhibition is local while excitation is both local and long- range. Specifically, a considerable amount of research on cortico-amygdala communication (coordination of sensory input between the auditory cortex and the lateral amygdala) relies on the reductionist view that the auditory cortex transmits only excitatory signals. However, it has long been known that long-range GABAergic neurons are important circuits element in many brain areas, such as the spiny projection neurons in the striatum and the Purkinje neurons in the cerebellum. Therefore, despite the fact that the existence of cortical long-range GABAergic neurons has been proven anatomically, previous studies have primarily focused on the local circuit organization of GABAergic interneurons, and inhibition is frequently described as being exclusively local. A growing body of evidence from our lab and others indicates that many of these long-range GABAergic projections arise from neurons expressing somatostatin, parvalbumin, and more recently from vasoactive intestinal peptide. Since somatostatin neurons form synapses primarily on the distal dendrites of target neurons, it has been suggested that this subpopulation of GABAergic cells plays a critical role modulating the plasticity of incoming sensory inputs. Importantly, strong preliminary evidence from our labs show that somatostatin- expressing neurons project to the lateral amygdala (CLA-Som). This proposal aims at determining the circuit organization and behavioral relevance of CLA-Som neurons in fear learning driven by auditory signals. Specifically, this proposal will dissect the CLA-Som microcircuits and behavior responsible for cortical amygdala communication answering the following questions: What are the anatomical, electrophysiological, and gene expression properties of CLA-Som neurons? What is the impact of CLA-Som neurons on the amygdala network and which are the circuit mechanisms through which they produce inhibition? Which are the behavioral conditions that recruit CLA-Som neurons and their role in fear learning? These questions will be investigated using retrograde and optogenetic labeling, specific neuronal-tagging-physiological recordings, in vivo patch clamping and linear probe recordings, calcium imaging in freely moving mice, and pathway selective chemogentic tools during actual learning. Discoveries from this work will be significant because they will provide foundational knowledge regarding cortical modulation of fear learning, describe a new GABAergic cortical-amygdala pathway, and provide new therapeutic targets for neuropathologies involving anxiety and phobias.
项目摘要/摘要 正确的情绪反应的特点是两种主要力量的动态相互作用:激发和 抑制力。目前认为,由局部GABA能中间神经元介导的抑制功能障碍会导致 广泛的精神病理,包括恐惧症和焦虑症。这是一项行之有效的原则 情绪学习背后的回路组织是抑制是局部的,而兴奋是局部的和长时间的-- 射程。具体地说,大量关于皮质-杏仁核通讯的研究(协调 听觉皮质和杏仁外侧核之间的感觉输入)依赖于简化论者的观点 听觉皮质只传递兴奋性信号。然而,人们很早就知道,远程伽玛能 神经元是许多脑区的重要回路元件,如大脑中的棘突投射神经元。 纹状体和小脑中的浦肯野神经元。因此,尽管大脑皮层存在 长程GABA能神经元已被解剖学证实,以往的研究主要集中在 GABA能中间神经元的局部回路组织,抑制经常被描述为独有的 当地人。来自我们实验室和其他实验室的越来越多的证据表明,许多这些远程伽玛能 投射来自表达生长抑素、小白蛋白的神经元,最近还来自血管活性物质 肠肽。由于生长抑素神经元主要在靶神经元的远侧树突上形成突触, 已有研究表明,这一亚群的GABA能细胞在调节细胞的可塑性方面起着关键作用。 传入的感官输入。重要的是,来自我们实验室的强有力的初步证据表明生长抑素- 表达神经元投射到杏仁外侧核(CLA-Som)。这项建议旨在确定巡回法庭 听觉信号驱动的恐惧学习中CLA-SOM神经元的组织和行为相关性。 具体地说,这项提案将剖析负责杏仁皮质的CLA-SOM微电路和行为 回答以下问题的交流:什么是解剖学、电生理学和基因 CLA-Som神经元的表达特性?CLA-SOM神经元对杏仁核网络和 它们产生抑制的电路机制是什么?哪些是行为条件, 招募CLA-SOM神经元及其在恐惧学习中的作用?这些问题将使用逆行和 光遗传标记、特定神经元标记-生理记录、活体膜片钳和线性探针 记录,自由活动小鼠的钙成像,以及实际过程中的路径选择化学工具 学习。这项工作的发现将具有重要意义,因为它们将提供基础知识 关于恐惧学习的皮质调节,描述了一种新的GABA能皮质-杏仁核通路,以及 为涉及焦虑和恐惧症的神经病理提供新的治疗靶点。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Alfonso J Apicella其他文献

Alfonso J Apicella的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Alfonso J Apicella', 18)}}的其他基金

Cortical Circuits of Interhemispheric Communication
半球间通讯的皮层回路
  • 批准号:
    9888369
  • 财政年份:
    2017
  • 资助金额:
    $ 59.04万
  • 项目类别:
Cortical Circuits of Interhemispheric Communication
半球间通讯的皮层回路
  • 批准号:
    9278413
  • 财政年份:
    2017
  • 资助金额:
    $ 59.04万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了