Evidence that disinhibition is associated with a decrease in number of vesicles available for release at inhibitory synapses

We used three-dimensional reconstruction from serial electron micrographs to investigate two structural changes that could underlie estrogen-induced disinhibition of hippocampal CA1 pyramidal cells: a decrease in the number of inhibitory inputs per neuron and/or a change in inhibitory boutons that could limit GABA release. We analyzed 373 boutons forming 510 inhibitory synapses in estrogen-treated and control animals. Our results show that estrogen specifically decreases the number of synaptic vesicles adjacent to the presynaptic membrane of inhibitory synapses without affecting the overall number of vesicles. We detected no difference in the density of inhibitory inputs. These findings provide a novel mechanism for the functional effects of estrogen on synaptic inhibition and represent the first in vivo evidence that the number of presynaptic vesicles available for release is a regulated property of synapses that affects synaptic physiology.