G protein-coupled oestrogen receptor 1 (GPER1) is expressed in hippocampal dendritic spines and axon terminals, but its role in long-term depression (LTD) is not known. Here, 17β-estradiol (E2) activation of GPER1 in CA3 resulted in the release of brain-derived neurotrophic factor and the local translation of activity-regulated cytoskeleton-associated protein (ARC). This increase in ARC levels led to the internalization and proteasome-mediated degradation of GluA1-containing AMPA receptors, and LTD, thus revealing a novel way in which E2 can mediate synaptic plasticity in the hippocampus.
Briz, V. et al. A novel form of synaptic plasticity in field CA3 of hippocampus requires GPER1 activation and BDNF release. J. Cell Biol. 210, 1225–1237 (2015)
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Lewis, S. Neurotrophic memory. Nat Rev Neurosci 16, 646 (2015). https://doi.org/10.1038/nrn4049