Dissecting the role of long range prefrontal circuits in early-life stress induced susceptibility

剖析长程前额叶回路在早期压力诱发的易感性中的作用

• 批准号: 10212933
• 负责人: Piray Atsak
• 金额: $ 18.24万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10212933
• 关键词: Adult; Affect; Amygdaloid structure; Animals; Anxiety Disorders; Behavior; Behavioral; Body Weight decreased; Brain; Brain region; Child; Chronic; Communication; Data; Development; Dissection; Elderly; Electrophysiology (science); Exposure to; Female; Gene Expression Profile; Goals; Grant; Hippocampus (Brain); Human; Individual Differences; Lead; Life; Literature; Measures; Medial; Mediating; Mental Depression; Mental disorders; Mentored Research Scientist Development Award; Mentorship; Methods; Modeling; Mood Disorders; Mus; Neurosciences; Nucleus Accumbens; Pathology; Pathway interactions; Personality Disorders; Phenotype; Physiology; Positioning Attribute; Predisposition; Prefrontal Cortex; Psychopathology; Recording of previous events; Reporting; Research; Research Proposals; Rewards; Risk; Risk Factors; Role; Site; Social Interaction; Stress; Stressful Event; Structure; Symptoms; Synaptic Transmission; System; Testing; Training; Universities; Work; base; biological adaptation to stress; career; childhood adversity; depressive symptoms; early life stress; experience; experimental study; in vivo; insight; male; maternal separation; mouse model; neural circuit; neuromechanism; neurophysiology; new therapeutic target; novel; postnatal; prevent; programs; relating to nervous system; resilience; response; social; social defeat; stress resilience

My career goal is to become an expert on the circuit level mechanisms of neural transmission underlying developmental stress and individual differences in stress response and sensitivity. I plan to lead a research lab studying the neurophysiological mechanisms of early-life stress (ELS) and the emergence of individual differences in adult stress response. ELS creates long-term risk to depression and anxiety disorders, particularly after facing stressful events during adulthood. However, little is known about how ELS produces sustained changes at the neural circuitry level that increase sensitivity to stress later in life. This kind of detailed circuit dissection cannot be performed in humans, thus by using a recently established two-hit model of early-life and adult stress in mice in which stress during a specific postnatal window increases the likelihood of adulthood stress to induce depressive-like behaviors. With this K01 grant and under the mentorship of Dr. Rene Hen at RFMH and Columbia University, I will test the role of long-range prefrontal circuits in the ELS-induced susceptibility to adult stress. I will combine an established two-hit mouse model of stress with advanced methods such as multi-site electrophysiological recordings and intersectional approaches for pathway specific chemogenetic manipulations. These studies represent a number of firsts in the developmental/systems neuroscience field: 1) the first to test the role of some of the long-range prefrontal cortex associated circuits (prefrontal-accumbens, amygdala, ventral hippocampus) activity and communication in stress susceptibility; 2) the first to dissect neural circuit activity and communication underlying the ELS-induced changes in adult stress response; 3) the first to investigate the impact of ELS in stress-susceptibility and underlying neural circuits in females; 4) the first to combine developmental stress with simultaneous multi-site recordings and intersectional approaches for pathway specific manipulations. These studies represent a significant career change and research redirection for me. This K01 award will afford me the mentorship and additional training that will prepare me to achieve my career goals and establish an independent research program geared towards investigating the neural circuits of which ELS leads to lifelong susceptibility to depression and psychiatric disorders.

我的职业目标是成为神经回路层面机制的专家