ESTRADIOL INCREASES THE SENSITIVITY OF HIPPOCAMPAL CA1 PYRAMIDAL CELLS TO NMDA RECEPTOR-MEDIATED SYNAPTIC INPUT - CORRELATION WITH DENDRITIC SPINE DENSITY

Previous studies have shown that estradiol induces new dendritic spine s and synapses on hippocampal CA1 pyramidal cells. We have assessed th e consequences of estradiol-induced dendritic spines on CA1 pyramidal cell intrinsic and synaptic electrophysiological properties. Hippocamp al slices were prepared from ovariectomized rats treated with either e stradiol or oil vehicle. CA1 pyramidal cells were recorded and injecte d with biocytin to visualize spines. The association of dendritic spin e density and electrophysiological parameters for each cell was then t ested using linear regression analysis. We found a negative relationsh ip between spine density and input resistance; however, no other intri nsic property measured was significantly associated with dendritic spi ne density. Glutamate receptor autoradiography demonstrated an estradi ol-induced increase in binding to NMDA, but not AMPA, receptors. We th en used input/output (I/O) curves (EPSP slope vs stimulus intensity) t o determine whether the sensitivity of CAI pyramidal cells to synaptic input is correlated with dendritic spine density. Consistent with the lack of an estradiol effect on AMPA receptor binding, we observed no relationship between the slope of an I/O curve generated under standar d recording conditions, in which the AMPA receptor dominates the EPSP, and spine density. However, recording the pharmacologically isolated NMDA receptor-mediated component of the EPSP revealed a significant co rrelation between I/O slope and spine density. These results indicate that, in parallel with estradiol-induced increases in spine/synapse de nsity and NMDA receptor binding, estradiol treatment increases sensiti vity of CA1 pyramidal cells to NMDA receptor-mediated synaptic input; further, sensitivity to NMDA receptor-mediated synaptic input is well correlated with dendritic spine density.