title: A novel form of synaptic plasticity in field CA3 of hippocampus requires GPER1 activation and BDNF release.
abstract: Estrogen is an important modulator of hippocampal synaptic plasticity and memory consolidation through its rapid action on membrane-associated receptors. Here, we found that both estradiol and the G-protein-coupled estrogen receptor 1 (GPER1) specific agonist G1 rapidly induce brain-derived neurotrophic factor (BDNF) release, leading to transient stimulation of activity-regulated cytoskeleton-associated (Arc) protein translation and GluA1-containing AMPA receptor internalization in field CA3 of hippocampus. We also show that type-I metabotropic glutamate receptor (mGluR) activation does not induce Arc translation nor long-term depression (LTD) at the mossy fiber pathway, as opposed to its effects in CA1, and it only triggers LTD after GPER1 stimulation. Furthermore, this form of mGluR-dependent LTD is associated with ubiquitination and proteasome-mediated degradation of GluA1, and is prevented by proteasome inhibition. Overall, our study identifies a novel mechanism by which estrogen and BDNF regulate hippocampal synaptic plasticity in the adult brain.
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766 VIB Center for the Biology of Disease, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Victor
authors.initials: V
authors.lastname: Briz
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766 College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766 Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Traditional Chinese Medicine, Hefei 230038, China.
authors.forename: Guoqi
authors.initials: G
authors.lastname: Zhu
authors.affiliation: College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Bi
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766 mbaudry@westernu.edu.
authors.forename: Michel
authors.initials: M
authors.lastname: Baudry
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D046988:Proteasome Endopeptidase Complex; D018091:Receptors, AMPA; D043562:Receptors, G-Protein-Coupled; D018094:Receptors, Metabotropic Glutamate; C520305:Gper1 protein, rat; C104077:metabotropic glutamate receptor type 1