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Role of Neural Activity and Perineuronal Nets in Adolescent Intermittent Ethanol-Induced Social Anxiety

神经活动和神经周围网络在青少年间歇性乙醇引起的社交焦虑中的作用

基本信息

批准号：
10314210
负责人：
Trevor Towner
金额：
$ 3.12万
依托单位：
STATE UNIVERSITY OF NY,BINGHAMTON
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：
2021-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10314210
关键词：
Adolescence Adolescent Adult Alcohols Animals Behavioral Brain Data Development Ethanol Ethanol dependence Evaluation Exposure to Extracellular Matrix Foundations Functional disorder Glutamates Goals Histocytochemistry Histology Image Analysis Insula of Reil Interneurons Investigation Knowledge Label LacZ Genes Medial Microscopy Neurobiology Neurons Operative Surgical Procedures Parvalbumins Pattern Play Population Positioning Attribute Postdoctoral Fellow Prefrontal Cortex Procedures Process Rattus Regulation Reporting Research Research Personnel Risk Factors Rodent Role Social Behavior Stimulus Substance abuse problem Synapses Techniques Testing Three-Dimensional Image Time Training Transgenic Organisms United States Up-Regulation Water adolescent alcohol exposure alcohol exposure alcohol measurement alcohol use disorder alcohol use initiation anxiety-like behavior anxious behavioral impairment behavioral outcome binge drinking career chemical genetics design developmental plasticity drinking drug of abuse emerging adulthood experimental study genetic manipulation glutamatergic signaling high school hippocampal pyramidal neuron indexing insight male neural circuit neurobiological mechanism neuromechanism neuronal cell body peer post-doctoral training pre-clinical research preference presynaptic relating to nervous system skills social social anxiety social deficits tool transmission process underage drinking

项目摘要

Project Summary Our research group has revealed long-lasting behavioral impairments associated with adolescent intermittent ethanol (AIE) exposure, with male rats exposed to ethanol during adolescence demonstrating social deficits indexed via decreases in social preference and social investigation. Our preliminary data point to the prelimbic (PrL) cortex as a region associated with this social inhibition. AIE has been reported to increase glutamatergic signaling in the PrL, potentially due to alterations in GABAergic transmission. PrL activity is heavily regulated by inhibitory parvalbumin (PV) interneurons that are often encompassed by extracellular matrix components, perineuronal nets (PNNs). This proposal is designed to test the hypothesis that AIE-induced dysfunction of the PrL is a result of PNN-dependent decreases of PV interneuron inhibitory control, a neural alteration that might directly contribute to social deficits evident in adult rats following AIE. This hypothesis will be tested in Aim 1 by determining whether inactivation of specific neural ensembles associated with responding to a social stimulus within the PrL can reverse AIE-induced social deficits. In Aim 2, we will assess the impact of AIE on PNN expression within the PrL and investigate whether AIE-dependent PNN alterations are associated with changes in glutamatergic and GABAergic inputs onto PV interneurons. For evaluation of the relationship between PNN upregulation and social alterations after AIE, we will test whether an enzymatic degradation of PNNs following AIE is able to reverse social deficits in AIE-exposed animals. Collectively, these studies will characterize specific neural mechanisms in the PrL that are disrupted following AIE and further our understanding of how these alterations contribute to social deficits. Through this training mechanism I will gain invaluable skills to build my technical tool kit, expand my theoretical framework, and further develop my conceptual research skillset, all of which will aid in my progression into postdoctoral training and eventually becoming an independent investigator.

项目总结