The study of stress on hippocampal synaptic plasticity and adult neurogenesis

Abstract

More evidence from animal and human study indicates that stressful life event may result in massive influence on cognitive function and behavior change based on the synaptic plasticity of hippocampus However the underlying cellular and molecular mechanism by which stress exerts it effects on behavior remain unclear Here we demonstrate several key regulator of hippocampal trisynaptic circuit which is sensitive to stress response The mossy fiber synapse onto hippocampal CA3 neurons shows unique molecular features and a wide dynamic range of plasticity An acute unpredictable and inescapable restraint tail-shock stress showed a marked impairment of long-term potentiation (LTP) expression in this region through a interruption of a cAMP-specific PDE4 activity Chronic stress has been found to suppress adult neurogenesis and we examined the influence of chronic social defeat stress (CSDS) on the morphological and electrophysiological properties of retrovirally-labeled adult-born dentate granule cells (DGCs) at different maturation stages Our results confirm that C57BL/6 inbred mouse strain subjected to CSDS can be separated into susceptible and unsusceptible subpopulations that displayed different levels of depressive-like behaviors but identical reductions in the survival and dendritic complexity of adult-born DGCs Combining electrophysiology with retrovirus- mediated birthdating and labeling we find that although CSDS does not alter the intrinsic electrophysiological properties and synaptic transmission of surviving adult-born DGCs it accelerates the developmental switch of synaptic N-methyl-D- aspartate receptors (NMDARs) from predominance of GluN2B- to GluN2A- containing receptors which in turn transforms the immature synapse of adult-born DGCs from one that exhibits enhanced LTP to one in which has normal levels of LTP Furthermore knockdown of the repressor element 1 silencing transcription factor (REST) in adult-born DGCs prevented CSDS-induced accelerated developmental switch of NMDAR subunit composition Together these results reveal a novel role for CSDS in regulating adult neurogenesis and suggest that CSDS may accelerate the rate of maturation of surviving adult-born DGCs through the expression of REST to overcome the neurotoxic effect

Date of Award	2014 Jun 27
Original language	English
Supervisor	Kuei-Sen Hsu (Supervisor)