Figure 8.

Schematic of the proposed molecular signaling involved in CRH-induced dendritic spine loss. The CRH receptor, CRHR1, is located on dendritic spine heads, within the postsynaptic density and in close proximity to NMDA- and AMPA-type ionotropic glutamate receptors. When CRH (released during stress from hippocampal interneurons), binds CRHR1 in the presence of network activity, this triggers an NMDA receptor-dependent signaling cascade that culminates in spine loss. Specifically, the influx of calcium ions through NMDA receptors activates calpain. Calpain cleaves actin-associated scaffolding proteins, such as spectrin, leading to the breakdown of the spine cytoskeleton and spine loss. The presence of GluR1 may protect subsets of mature spines from the actions of CRH.