title: Rapid increases in immature synapses parallel estrogen-induced hippocampal learning enhancements.
abstract: Dramatic increases in hippocampal spine synapse density are known to occur within minutes of estrogen exposure. Until now, it has been assumed that enhanced spinogenesis increased excitatory input received by the CA1 pyramidal neurons, but how this facilitated learning and memory was unclear. Delivery of 17β-estradiol or an estrogen receptor (ER)-α (but not ER-β) agonist into the dorsal hippocampus rapidly improved general discrimination learning in female mice. The same treatments increased CA1 dendritic spines in hippocampal sections over a time course consistent with the learning acquisition phase. Surprisingly, estrogen-activated spinogenesis was associated with a decrease in CA1 hippocampal excitatory input, rapidly and transiently reducing CA1 AMPA activity via a mechanism likely reflecting AMPA receptor internalization and creation of silent or immature synapses. We propose that estrogens promote hippocampally mediated learning via a mechanism resembling some of the broad features of normal development, an initial overproduction of functionally immature connections being subsequently "pruned" by experience.
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada N1G 2W1; Neuroscience Program, University of Guelph, Guelph, ON, Canada N1G 2W1;
authors.forename: Anna
authors.initials: A
authors.lastname: Phan
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada N1G 2W1; Neuroscience Program, University of Guelph, Guelph, ON, Canada N1G 2W1;
authors.forename: Sarah
authors.initials: S
authors.lastname: Suschkov
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada N1G 2W1; Neuroscience Program, University of Guelph, Guelph, ON, Canada N1G 2W1;
authors.forename: Luke
authors.initials: L
authors.lastname: Molinaro
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada N1G 2W1; Neuroscience Program, University of Guelph, Guelph, ON, Canada N1G 2W1;
authors.forename: Kathryn
authors.initials: K
authors.lastname: Reynolds
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada N1G 2W1; Neuroscience Program, University of Guelph, Guelph, ON, Canada N1G 2W1;
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Lymer
authors.affiliation: Neuroscience Program, University of Guelph, Guelph, ON, Canada N1G 2W1; Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1;
authors.forename: Craig D C
authors.initials: CD
authors.lastname: Bailey
authors.affiliation: Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10065.
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Kow
authors.affiliation: Neuroscience Program, University of Guelph, Guelph, ON, Canada N1G 2W1; Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1;
authors.forename: Neil J
authors.initials: NJ
authors.lastname: MacLusky
authors.affiliation: Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10065 pfaff@rockefeller.edu echoleri@uoguelph.ca.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Pfaff
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada N1G 2W1; Neuroscience Program, University of Guelph, Guelph, ON, Canada N1G 2W1; pfaff@rockefeller.edu echoleri@uoguelph.ca.
authors.forename: Elena
authors.initials: E
authors.lastname: Choleris
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology*; D049229:Dendritic Spines / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D007858:Learning / Q000187:drug effects*; D051379:Mice; D009474:Neurons / Q000502:physiology; D010052:Ovariectomy; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D013997:Time Factors
chemical_list: D004967:Estrogens; D018091:Receptors, AMPA; D004958:Estradiol
keywords: immature synapse; short-term memory; signal-to-noise ratio; structural plasticity; synaptic plasticity