Correlated memory defects and hippocampal dendritic spine loss after acute stress involve corticotropin-releasing hormone signaling

• DOI: 10.1073/pnas.1003825107
• Publication Date: 2010-07-07T02:23:58Z
• Authors: Yuncai Chen; Christopher S. Rex; Courtney J. Rice; Céline M. Dubé; Christine M. Gall; Gary Lynch; Tallie Z. Baram
• Keywords: Male; 0301 basic medicine; Time Factors; hippocampus; Corticotropin-Releasing Hormone; Dendritic Spines; Biological Psychology; Long-Term Potentiation; 610; Stress; Basic Behavioral and Social Science; Hippocampus; memory; Mice; 03 medical and health sciences; Cognition; Memory; 616; Behavioral and Social Science; Psychology; 2.1 Biological and endogenous factors; Animals; long-term potentiation; synaptic plasticity; Biomedical and Clinical Sciences; Neurosciences; corticotropin-releasing factor; Pharmacology and Pharmaceutical Sciences; Mental Health; Neurological; Synapses; Psychological; Mental health; Stress, Psychological; Signal Transduction

Stress affects the hippocampus, a brain region crucial for memory. In rodents, acute stress may reduce density of dendritic spines, the location of postsynaptic elements of excitatory synapses, and impair long-term potentiation and memory. Steroid stress hormones and neurotransmitters have been implicated in the underlying mechanisms, but the role of corticotropin-releasing hormone (CRH), a hypothalamic hormone also released during stress within hippocampus, has not been elucidated. In addition, the causal relationship of spine loss and memory defects after acute stress is unclear. We used transgenic mice that expressed YFP in hippocampal neurons and found that a 5-h stress resulted in profound loss of learning and memory. This deficit was associated with selective disruption of long-term potentiation and of dendritic spine integrity in commissural/associational pathways of hippocampal area CA3. The degree of memory deficit in individual mice correlated significantly with the reduced density of area CA3 apical dendritic spines in the same mice. Moreover, administration of the CRH receptor type 1 (CRFR 1 ) blocker NBI 30775 directly into the brain prevented the stress-induced spine loss and restored the stress-impaired cognitive functions. We conclude that acute, hours-long stress impairs learning and memory via mechanisms that disrupt the integrity of hippocampal dendritic spines. In addition, establishing the contribution of hippocampal CRH–CRFR 1 signaling to these processes highlights the complexity of the orchestrated mechanisms by which stress impacts hippocampal structure and function.