NMDA Receptor Activation and Calpain Contribute to Disruption of Dendritic Spines by the Stress Neuropeptide CRH

摘要: The complex effects of stress on learning and memory are mediated, in part, by stress-induced changes the composition structure excitatory synapses. In hippocampus, involve several factors including glucocorticoids stress-released neuropeptide corticotropin-releasing hormone (CRH), which influence integrity dendritic spines function synapses they carry. CRH, at nanomolar, presumed-stress levels, rapidly abolishes short-term synaptic plasticity destroys spines, yet mechanisms for these not fully understood. Here we tested hypothesis that glutamate receptor-mediated processes, shape function, engaged CRH contribute to spine destabilization. cultured rat hippocampal neurons, application reduced density a time- dose-dependent manner, this action depended receptor type 1. CRH-mediated loss required network activity activation NMDA, but AMPA receptors; indeed GluR1-containing were resistant CRH. Downstream NMDA receptors, calcium-dependent enzyme, calpain, was recruited, resulting breakdown actin-interacting proteins spectrin. Pharmacological approaches demonstrated calpain recruitment contributed critically CRH-induced loss. conclusion, co-opts synapses, leading selective spines. This might as an adaptive mechanism preventing consequences adverse memories associated with severe stress.