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The Neural Basis of Social Stress-induced Depression

社会压力诱发抑郁症的神经基础

基本信息

批准号：
8956803
负责人：
Byungkook Lim
金额：
$ 49.27万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-10 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8956803
关键词：
Address Adult Adverse effects Affect Amygdaloid structure Anhedonia Animals Area Aversive Stimulus Behavior Behavioral Brain Cells Cognitive Data Depressive disorder Desire for food Diagnosis Disease Electrophysiology (science)Fiber Genetic Engineering Globus Pallidus Goals Habenula Human Hypothalamic structure Injection of therapeutic agent Investigation Investments Knowledge Lateral Link Major Depressive Disorder Mediating Mental Depression Mental disorders Methods Monitor Motivation Mus Neurons Parvalbumins Patients Pattern Phenotype Photometry Physiological Population Prevalence Property Psychomotor Impairments Research Rewards Rodent Role Sleep Social Interaction Staging Stimulus Stress Structure Symptoms Synapses Techniques Testing Therapeutic Time Tracer United States Ventral Tegmental Area Viral Work anatomical tracing base calcium indicator cell type cholinergic neuron depressed patient depressive behavior depressive symptoms effective therapy experience in vivo in vivo imaging neural circuit neuromechanism neuropsychiatry novel strategies optogenetics patch clamp pleasure public health relevance relating to nervous system response reward circuitry social social stress tool

项目摘要

DESCRIPTION (provided by applicant): Despite the increased prevalence of major depressive disorder (MDD) and the continued investment into identifying effective cures, most treatments merely alleviate symptoms rather than addressing causes. Long-term treatments are generally required for this disease and often include many side-effects. The onset of depression is often precipitated by stressful and/or aversive stimuli. Animals, too, are susceptible to the effects of stress. For example, repeated social defeat stress in rodents induces pervasive and long-lasting behavioral changes similar to the symptoms seen in patients with MDD including impaired social interaction, lack of motivation, helplessness and anhedonia. While the behavioral changes associated with depression have been well-studied, there is relatively little knowledge about the accompanying changes in the neural circuitry. Thus, we will anatomically and functionally dissect the distinct neural circuits mediating various stress-induced behaviors in mice to better understand the mechanistic changes in the brain accompanying MDD in human patients, which will help to devise revolutionary circuit-specific and stage-specific diagnosis and treatments. To accomplish this, we will examine the neural circuit mechanism of ventral pallidum (VP), one of the major components of reward circuitry, underlying depressive behaviors elicited by repeated social defeat stress in combination with a variety techniques to address circuit-level mechanisms, including optogenetics, viral mediated tracing, electrophysiology, and real time in vivo fiber photometry. Our preliminary findings showed that different types of neurons in VP project to different target structures which may be involved in different aspects of depressive behaviors. First, we will define the projection specific roles of VP circuity in depressive behaviors induced by repeated social defeat stress using optogenetics and viral tracing methods. Second, using in vivo fiber photometry and newly developed viral tools, we will directly monitor the dynamics of neural activity of VP circuitry in cell-type and projection specific manner in vivo in real time during social interaction before and after the repeated social defeat stress, and their response to anti-depressant treatment. Third, using ex vivo electrophysiology analysis we will examine the circuit-specific electrophysiological and synaptic changes induced by the stress. The accomplishment of the proposed works will be greatly beneficial to both the research and treatment of MDD, and will also provide a fundamental framework for studying mental disorders in circuit-specific manner.