Estrogen and Synapses in the Hippocampus

Our research is devoted to understanding how the hormone, estrogen, influences the structure and function of synapses, particularly in the hippocampus. The hippocampus is a part of the brain important in learning and memory, and that is frequently a focus of seizure activity in epilepsy. My early work focused on estrogen‐induced changes in excitatory synaptic connectivity. Our recent studies, however, have shown that estrogen also exerts powerful effects on inhibitory synapses in the hippocampus. A combination of light microscopy, serial section electron microscopy, electrophysiological recording, and behavioral analyses has shown that: 1. Immunoreactivity for classical estrogen receptor protein is found both in the nucleus of some inhibitory neurons and also on presynaptic vesicles at inhibitory synapses. 2. Estrogen transiently suppresses inhibitory synaptic transmission by decreasing the number of neurotransmitter vesicles docked at presynaptic active zones; this synaptic change is paralleled by increased susceptibility to hippocampus‐dependent seizures. 3. At the same time, however, estrogen also upregulates hippocampal neuropeptide Y, and facilitates its release during severe seizure activity, which serves to limit the duration of severe seizures. Together, these studies reveal novel effects of estrogen on the structure and function of inhibitory synapses in the hippocampus that are associated with profound differences in hippocampus‐dependent behavior.