Estradiol acutely potentiates hippocampal excitatory synaptic transmission through a presynaptic mechanism.
Although recent evidence suggests that the hippocampus is a source of 17β-estradiol (E2), the physiological role of this neurosteroid E2, as distinct from ovarian E2, is unknown. One likely function of neurosteroid E2 is to acutely potentiate excitatory synaptic transmission, but the mechanism of this effect is not well understood. Using whole-cell voltage-clamp recording of synaptically evoked EPSCs in adult rat hippocampal slices, we show that, in contrast to the conclusions of previous studies, E2 potentiates excitatory transmission through a presynaptic mechanism. We find that E2 acutely potentiates EPSCs by increasing the probability of glutamate release specifically at inputs with low initial release probability. This effect is mediated by estrogen receptor β (ERβ) acting as a monomer, whereas ERα is not required. We further show that the E2-induced increase in glutamate release is attributable primarily to increased individual vesicle release probability and is associated with higher average cleft glutamate concentration. These two findings together argue strongly that E2 promotes multivesicular release, which has not been shown before in the adult hippocampus. The rapid time course of acute EPSC potentiation and its concentration dependence suggest that locally synthesized neurosteroid E2 may activate this effect in vivo.
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA.
Tereza
T
Smejkalova
Catherine S
CS
Woolley
D000818:Animals; D004958:Estradiol / Q000008:administration & dosage* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D004958:Estradiol