Estrogen Regulates Functional Inhibition of Hippocampal CA1 Pyramidal Cells in the Adult Female Rat

Abstract

Previous studies have focused considerable attention on the effects of estrogen on excitatory synaptic input to hippocampal CA1 pyramidal cells. Estrogen increases the density of dendritic spines and synapses on CA1 pyramidal cells and increases the sensitivity of these cells to excitatory synaptic input. Little is known, however, about the effects of estrogen on inhibitory synaptic input to CA1 pyramidal cells. We have used immunohistochemistry for glutamic acid decarboxylase and whole-cell voltage-clamp recording of IPSCs and EPSCs at multiple time points after estrogen treatment to (1) investigate estrogen regulation of synaptic inhibition in CA1 and (2) evaluate how estrogen affects the interaction between inhibitory and excitatory input to CA1 pyramidal cells. We find that estrogen transiently suppresses GABA(A)-mediated inhibition of CA1 pyramidal cells at a time point before changes in excitatory input to these cells occur. This finding is consistent with the suggestion that transient disinhibition of CA1 pyramidal cells is involved in estrogen-induced dendritic spine formation. We have also found that at a later time after estrogen, inhibition of CA1 pyramidal cells recovers in parallel with enhancement of NMDA-mediated excitatory input. The concurrent enhancement of GABA(A) and NMDA-mediated input to CA1 pyramidal cells restores a balance of excitatory and inhibitory input to these cells and increases the potential dynamic range of CA1 pyramidal cell responses to synaptic input.