The role of distinct hippocampal calbindin neurons in modulating individual susceptibility to early life stress

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Early-life stress is a major risk factor for psychiatric disorders including major depressive disorder. However, the neurobiological mechanisms underlying the deleterious effects of early-life stress remain to be elucidated. The Chinese and German research teams applying for this project have been collaborating on the mechanistic studies of the neurobiology of early-life stress, and have accumulated solid and exciting data. The two teams have jointly published over 10 papers in internationally renowned journals including Nature Neuroscience, Biological Psychiatry and Neuropsychopharmacology. This project focuses on calbindin, a calcium-binding protein closely related to neural plasticity and implicated in psychiatric disorders. Combining chemogenetic, molecular, morphological, pharmacological, and behavioral approaches, this project aims to reveal the regulation of hippocampal calbindin protein expression and the activity of calbindin-expressing neuronal subpopulations by key stress mediators especially the GR-FKBP51 and CRHR1-nectin-3 systems. Moreover, the involvement of distinct hippocampal calbindin-expressing neuronal subpopulations in early-life stress-impaired synaptic plasticity as well as emotional and cognitive behavior will be dissected. This study will shed new light on the underlying mechanisms of stress-related psychiatric disorders and the development of therapeutic targets.