Abstract
Stress is ubiquitous in modern life and exerts profound effects on cognitive and emotional functions. Thus, whereas acute stress enhances memory, longer episodes exert negative effects through as yet unresolved mechanisms. We report a novel, hippocampus-intrinsic mechanism for the selective memory defects that are provoked by stress. CRH (corticotropin-releasing hormone), a peptide released from hippocampal neurons during stress, depressed synaptic transmission, blocked activity-induced polymerization of spine actin and impaired synaptic plasticity in adult hippocampal slices. Live, multiphoton imaging demonstrated a selective vulnerability of thin dendritic spines to this stress hormone, resulting in depletion of small, potentiation-ready excitatory synapses. The underlying molecular mechanisms required activation and signaling of the actin-regulating small GTPase, RhoA. These results implicate the selective loss of dendritic spine sub-populations as a novel structural and functional foundation for the clinically important effects of stress on cognitive and emotional processes.
Highlights
CRH-treated slices, we evaluated the actions of the CRH (100 nM) led to selective and progressive disappeptide on dendritic spines that carry the postsynap- pearance of thin spines over the same time course tic elements of excitatory synapses in hippocampal (Figure 3c)
A large body of literature has focused on the role of steroid stress hormone on the structure and function of hippocampal neurons, dendritic spines and synapses,[1,2,3,5,6,9,11,51,52] leading to the discovery of novel molecular mechanisms.[53,54]
Brief application of CRH primes and augments LTP59,60 through CRH receptor 1 (CRHR1) signaling and enhances memory.[3,58,59,61]
Summary
Y Chen[1], EA Kramar[2], LY Chen[2], AH Babayan[2], AL Andres[2], CM Gall[2], G Lynch[2,3] and TZ Baram[1,2,4]. Stress is ubiquitous in modern life and exerts profound effects on cognitive and emotional functions. Whereas acute stress enhances memory, longer episodes exert negative effects through as yet unresolved mechanisms. Hippocampus-intrinsic mechanism for the selective memory defects that are provoked by stress. Multiphoton imaging demonstrated a selective vulnerability of thin dendritic spines to this stress hormone, resulting in depletion of small, potentiation-ready excitatory synapses. The underlying molecular mechanisms required activation and signaling of the actin-regulating small GTPase, RhoA. These results implicate the selective loss of dendritic spine sub-populations as a novel structural and functional foundation for the clinically important effects of stress on cognitive and emotional processes. Molecular Psychiatry (2013) 18, 485–496; doi:10.1038/mp.2012.17; published online 13 March 2012
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