Deconstructing the cellular control of hippocampal functions related to mental health: a role for birth order.

解构与心理健康相关的海马功能的细胞控制：出生顺序的作用。

• 批准号: 10056224
• 负责人: ALEX DRANOVSKY
• 金额: $ 68.29万
• 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: 2019-01-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10056224
• 关键词: Adolescent; Adrenal Glands; Adult; Alzheimer' s Disease; American; Anesthesia procedures; Animals; Antidepressive Agents; Anxiety; Behavior; Behavioral; Biology; Birth; Birth Order; Brain; Cell Lineage; Cell physiology; Cells; Chronic stress; Complex; Date of birth; Development; Disease; Distal; Dorsal; Environmental Exposure; Exercise; Exhibits; Exposure to; Functional disorder; Genetic; Glial Fibrillary Acidic Protein; Glucocorticoid Receptor; Glucocorticoids; Hilar; Hippocampus (Brain); Hormones; Human; Hypoxemia; Infection; Injury; Learning; Life; Link; Logic; Memory; Mental Depression; Mental Health; Mental disorders; Mineralocorticoid Receptor; Modeling; Mus; Mutation; Neonatal; Neurons; Outcome; Parahippocampal Gyrus; Pathology; Performance; Pharmacogenetics; Phenotype; Physiological; Physiology; Population; Process; Psychosocial Stress; Rabies virus; Regulation; Research Personnel; Rodent; Role; Schizophrenia; Series; Slice; Stress; Structure; Supporting Cell; Synapses; System; Techniques; Testing; Thinking; Toxicant exposure; Trauma; Work; acute stress; adult neurogenesis; adult stem cell; base; behavioral response; biological adaptation to stress; cellular targeting; cohort; dentate gyrus; depressive behavior; design; drug of abuse; environmental change; environmental enrichment for laboratory animals; experience; experimental study; genetic approach; hormone regulation; improved; interest; nerve stem cell; neurogenesis; neuropsychiatric disorder; optogenetics; periadolescent; postnatal; postnatal development; relating to nervous system; resilience; response; sensor; spatial memory; stem cell proliferation; stem cells; stress resilience

The hippocampus has been implicated in the biology of stress as both a stress sensor and a regulator of the stress response. It exhibits the brain's highest concentration of glucocorticoid and mineralocorticoid receptors, as well as extensive structural and physiological plasticity in response to chronic stress exposure7. The hippocampus is also involved in encoding context, learning and memory, and has been repeatedly implicated in performance on depression and anxiety-related tasks in rodents and humans. Hence, it is no surprise that hippocampal pathology has been attributed to a wide range of psychiatric diseases like Schizophrenia, depression, anxiety, and Alzheimer's disease. Within the hippocampus, a postnatal neural stem cell system is exquisitely sensitive to environmental changes including stressful and enriching experiences. Exposure to chronic stress decreases neurogenesis and increases the proliferation of stem cells, while exposure to environmental enrichment, exercise, and antidepressants increases neurogenesis without impacting stem cells. While hippocampal neurogenesis is highly sensitive to environmental manipulations, the resulting neurons are thought to contribute to all of the hippocampal functions described above including stress regulation. Thus, neurons that support diverse functions are born continuously throughout postnatal development and this process of neurogenesis is sensitive to stress and to other environmental changes. We are interested in unraveling the cellular logic supporting the functional repertoire of the hippocampal dentate gyrus. Studies outlined in this proposal aim to identify cells within the dentate gyrus of the hippocampus that are important for each of the hippocampal functions. We will use a series of state of the art genetic approaches for targeting discrete populations of dentate gyrus neurons as they would be by stress during development and then examine how each population of cells contributes to normal hippocampal functioning and circuitry. Completing the proposed studies will help decipher which hippocampal neurons contribute to encoding stress responses and determine whether the same or different cells support other hippocampal functions.

海马体在压力的生物学中被认为既是压力传感器又是压力调节器