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Serotonin modulation of the development of neural circuits underlying reward processing and impulsivity in adolescents

血清素对青少年奖励处理和冲动神经回路发育的调节

基本信息

批准号：
10569661
负责人：
Katherine M Nautiyal
金额：
$ 55.53万
依托单位：
DARTMOUTH COLLEGE
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：
2021-04-01 至 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10569661
关键词：
Address Adolescence Adolescent Adolescent Development Adult Aggressive behavior Anxiety Attention deficit hyperactivity disorder Automobile Driving Award Basic Science Behavior Behavioral Behavioral Mechanisms Biological Borderline Personality Disorder Brain Calcium Cells Complex Corpus striatum structure Data Development Disease Etiology Event Funding Goals Home Impulsive Behavior Impulsivity Individual Intervention Knock-out Knowledge Learning Long-Term Depression Measures Mediating Mental Depression Mental disorders Methods Molecular Mouse Cell Line Mus National Institute of Mental Health Nature Neuromodulator Neurons Obsessive-Compulsive Disorder Operant Conditioning Outcome Pathologic Pathology Pharmacotherapy Phenotype Prevention Process Research Research Personnel Research Project Grants Rewards Rodent Role Schizophrenia Scientist Serotonin Serotonin Receptor 5-HT1B Shapes Signal Transduction Stimulus Strategic Planning Synapses System Techniques Technology Testing Time Transgenic Mice Work addiction behavior test behavioral phenotyping biobehavior career cell type cognitive development experimental study genetic manipulation high reward high risk in vivo calcium imaging innovation longitudinal human study microendoscope neural neural circuit neurodevelopment neuromechanism novel prevent programs response reward processing suicidal

项目摘要

PROJECT SUMMARY The goal of this proposal for the Biobehavioral Research Awards for Innovative New Scientists (BRAINS) program is to understand typical and atypical adolescent development of reward processing and impulsive behavior. These complex phenotypes are found in many psychiatric disorders including attention deficit hyperactivity disorder, borderline personality disorder, and schizophrenia. Adolescence is a sensitive period for the emergence of dysregulated reward processing and disordered impulsivity, and for the development of underlying neural circuits thought to be responsible. However, it is unclear what factors push development towards pathological trajectories and it is unknown how pathology is encoded by changes in neural circuits. The Adolescent Brain Cognitive Development (ABCD) longitudinal study of human brain and behavior is underway to identify factors in adolescence that predict impulsivity and other reward-related phenotypes. Similar longitudinal data from mice are necessary to allow molecular, cellular, and circuit-level interrogation of adolescent development. This knowledge is critical for targeted interventions to alter and prevent developmental pathology. This proposal develops a framework for mouse ABCD studies. We use an innovative approach to measure complex behavioral phenotypes in the homecage that allows for testing on a timescale compatible with assessing the dynamic changes during adolescence. This proposal focuses on the role of serotonin modulation of corticostriatal projections in driving adolescent maturation of reward processing and impulsivity. Using transgenic mouse lines for cell-type and time period-specific manipulations, we will investigate circuit-level mechanisms of serotonin modulation of adolescent developmental trajectories. The high-risk, high-reward use of in vivo calcium imaging in adolescents will uncover the single cell and ensemble- level changes occurring in the adolescent brain that supports adolescent behavioral maturation. Using microendoscope technology we will identify neural changes at the cellular level throughout adolescence, and define a trajectory of pathological development. These studies will point to a timeframe and mechanism for targeted prevention and treatment of developmental pathology related to reward processing and impulsivity. Our results will inform refinement of pharmacotherapies aimed at modulating serotonin signaling in adolescents for the treatment of depression, anxiety, and obsessive compulsive disorder. This research project is highly appropriate for BRAINS funding because it directly addresses two key objectives in the NIMH Strategic Plan and applies novel methods and techniques to advance our understanding of the major conceptual question of what drives adolescent maturation. As an early career investigator, funding for this ambitious proposal, which I’m uniquely equipped to carry out, would allow me to launch an innovative basic research program aimed at understanding the atypical development of reward processing and impulsivity.

项目总结