Virtually all mental and some medical illnesses are exacerbated by stressful experiences, while social enrichment offers protection. Disorders linked to stress exposure like affective and anxiety disorders are some of the most prevalent diseases in the United States and throughout the world. Depression and anxiety often affect young individuals, cause years of lost productivity, and impose a tremendous public health burden. Stress confers vulnerability to genetic risks for major depressive disorder during distinct sensitive developmental periods. Unfortunately, the cellular and molecular mechanisms by which time-restricted environmental exposures produce delayed and sustained effects on mood, affect, anxiety, and other dimensions of mental functioning are poorly understood. In both rodents and humans, stress dramatically suppresses adult hippocampal neurogenesis. Moreover, the lasting effects of stress on adult stem cell function can vary greatly depending on the animal's age at the time of exposure. We recently discovered that in adult mice, chronic stress increases the number of neural stem cells. Young neurons generated by these stem cells are implicated in behavioral and physiological responses to chronic stress. Studies outlined in this proposal aim to identify the cells that are important in governing hippocampal response to stress. We will use a series of 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.
Millions of Americans suffer from depression, anxiety, and other disorders related to stress exposure. Exposure to stress, especially during sensitive periods in development, can have life-long consequences for mental health, yet the mechanisms by which stress produces lasting changes in the brain are still poorly understood. By identifying the cells that encode stress and their role in developmental consequences of stress exposure as outlined in this proposal, we hope to identify targets to counter the detrimental effects of stress on mental health and confer resilience.
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