The role of basal forebrain GABAergic neurons in fear expression and inhibition.

基底前脑 GABA 能神经元在恐惧表达和抑制中的作用。

基本信息

批准号：
10428746
负责人：
Ciorana Roman Ortiz
金额：
$ 0.78万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
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：
2021-07-31 至 2021-10-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10428746
关键词：
Address Amygdaloid structure Arousal Behavior Behavioral Behavioral Assay Biological Assay Brain Brain region Calcium Characteristics Complex Computing Methodologies Conflict (Psychology)Cues Data Decision Making Detection Disease Educational process of instructing Electrophysiology (science)Environment Extinction (Psychology)Fellowship Foundations Freezing Fright Grant Image In Vitro Institution Knowledge Learning Measures Medial Mediating Memory Mental Health Mental disorders Mentors Motivation Neurons Neurosciences Pathway Analysis Pathway interactions Phase Population Post-Traumatic Stress Disorders Prefrontal Cortex Process Process Assessment Regulation Research Retrieval Risk Assessment Role Scientist Structure System Techniques Testing Time Training Writing basal forebrain behavioral outcome cell type computational neuroscience conditioned fear data modeling emotion dysregulation experience fear memory gamma-Aminobutyric Acid in vivo in vivo calcium imaging insight interest learning extinction memory process motivational processes neural circuit neural network neuromechanism neuronal circuitry novel optogenetics postsynaptic recruit relating to nervous system response tool vigilance

Address Amygdaloid structure Arousal Behavior Behavioral Behavioral Assay Biological Assay Brain Brain region Calcium Characteristics Complex Computing Methodologies Conflict (Psychology)Cues Data Decision Making Detection Disease Educational process of instructing Electrophysiology (science)Environment Extinction (Psychology)Fellowship Foundations Freezing Fright Grant Image In Vitro Institution Knowledge Learning Measures Medial Mediating Memory Mental Health Mental disorders Mentors Motivation Neurons Neurosciences Pathway Analysis Pathway interactions Phase Population Post-Traumatic Stress Disorders Prefrontal Cortex Process Process Assessment Regulation Research Retrieval Risk Assessment Role Scientist Structure System Techniques Testing Time Training Writing basal forebrain behavioral outcome cell type computational neuroscience conditioned fear data modeling emotion dysregulation experience fear memory gamma-Aminobutyric Acid in vivo in vivo calcium imaging insight interest learning extinction memory process motivational processes neural circuit neural network neuromechanism neuronal circuitry novel optogenetics postsynaptic recruit relating to nervous system response tool vigilance

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项目摘要

PROJECT SUMMARY Heightened threat response and dysregulation of emotional learning and memory are key characteristics of fear-related disorders such as post-traumatic stress disorder. The basal forebrain (BF) is considered a crucial structure in the regulation of fear learning and memory through the modulation of arousal, vigilance, and motivation salience. However, the role of specific BF cell types in the expression of conditioned fear behaviors remains unclear. Gamma-Aminobutyric acid (GABA)-containing neurons are one of the most abundant BF cell types, are activated in response to threat-predictive cues, and project broadly throughout the brain. More importantly they project to the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) which are essential brain regions in fear association and expression. In this proposal I will investigate the role of BF GABAergic neurons and their long-range projections in cued fear expression and inhibition. In Aim 1 I investigated the contribution of BF GABAergic activity on expression and extinction of cued fear memory. My research revealed a time-dependent role for this population in cue-evoked freezing, wherein GABAergic activity was required for memory expression at remote but not early time points after learning. For Aim 2 I will examine BF GABAergic projections to the BLA and mPFC during fear expression. For Exp. 2.1 and Exp. 2.2 I will use in vivo calcium imaging and optogenetic approaches to assesses the role basal forebrain projections to mPFC and BLA during cued fear memory expression. To examine the effect of BF GABAergic afferents in mPFC and BLA activity in Exp. 2.3, I will use in vitro electrophysiology. In Aim 3, I delineate plans for postdoctoral research, including the identification of a postdoctoral fellowship mentor and institution, and the use of computational methods to examine neural circuits in risk assessment behavioral assays. The results from this proposal will broaden our understanding on inhibitory circuits that underlie fear expression and provide an insight for how fear memory circuits shift at remote timepoints.

项目摘要情绪学习和记忆的威胁反应增强和失调是关键特征与恐惧有关的疾病，例如创伤后应激障碍。基础前脑（BF）被认为是至关重要的通过调节唤醒，警惕和调节恐惧学习和记忆的结构动机显着性。但是，特定BF细胞类型在条件恐惧行为表达中的作用仍然不清楚。 γ-氨基丁酸（GABA） - 含有最丰富的BF细胞之一响应威胁可预测性提示，并在整个大脑中广泛投影而激活类型。更多的重要的是，它们投射到内侧前额叶皮层（MPFC）和基底外侧杏仁核（BLA）恐惧关联和表达中的基本大脑区域。在此提案中，我将调查BF的作用 GABA能神经元及其在暗示恐惧表达和抑制作用中的远程预测。在目标1 i 研究了BF GABA能活性对提示恐惧记忆的表达和灭绝的贡献。我的研究揭示了该人群在提示诱发的冻结中的时间依赖性作用，其中gabaergic 学习后，需要在远程表达的内存表达，而不是早期时间点。对于目标2我会在恐惧表达过程中检查BF的BF GABA能预测。用于经验。 2.1和Exp。 2.2 i 将使用体内钙成像和光遗传学方法来评估基础前脑的投影 MPFC和BLA在提示恐惧记忆表达中。检查BF GABA能传入在 EXP中的MPFC和BLA活动。 2.3，我将使用体外电生理学。在AIM 3中，我描述了计划博士后研究，包括识别博士后奖学金导师和机构，以及使用计算方法在风险评估行为测定中检查神经回路。结果从这一提议中，我们将扩大我们对恐惧表达和抑制性电路的理解提供有关恐惧记忆电路如何在远程时间点转移的见解。