title: Estrous Cycle-Dependent Phasic Changes in the Stoichiometry of Hippocampal Synaptic AMPA Receptors in Rats.
abstract: Cognitive function can be affected by the estrous cycle. However, the effect of the estrous cycle on synaptic functions is poorly understood. Here we show that in female rats, inhibitory-avoidance (IA) task (hippocampus-dependent contextual fear-learning task) drives GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) into the hippocampal CA3-CA1 synapses during all periods of the estrous cycle except the proestrous period, when estrogen levels are high. In addition, IA task failed to drive CP-AMPARs into the CA3-CA1 synapses of ovariectomized rats only when estrogen was present. Thus, changes in the stoichiometry of AMPA receptors during learning depend on estrogen levels. Furthermore, the induction of long-term potentiation (LTP) after IA task was prevented during the proestrous period, while intact LTP is still expressed after IA task during other period of the estrous cycle. Consistent with this finding, rats conditioned by IA training failed to acquire hippocampus-dependent Y-maze task during the proestrous period. On the other hand, during other estrous period, rats were able to learn Y-maze task after IA conditioning. These results suggest that high estrogen levels prevent the IA learning-induced delivery of CP-AMPARs into hippocampal CA3-CA1 synapses and limit synaptic plasticity after IA task, thus preventing the acquisition of additional learning.
authors.affiliation: Department of Physiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Tada
authors.affiliation: Department of Physiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan; Department of Anesthesiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Koide
authors.affiliation: Department of Physiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Wakana
authors.initials: W
authors.lastname: Ara
authors.affiliation: Department of Physiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Department of Physiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan; Department of Physiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8511, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Funabashi
authors.affiliation: Department of Physiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Suyama
authors.affiliation: Department of Anesthesiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Physiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D010052:Ovariectomy; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013647:Task Performance and Analysis
chemical_list: D004967:Estrogens; D018091:Receptors, AMPA; D002118:Calcium