ESTRADIOL INCREASES THE FREQUENCY OF MULTIPLE SYNAPSE BOUTONS IN THE HIPPOCAMPAL CA1 REGION OF THE ADULT FEMALE RAT

The effect of estradiol to increase the density of dendritic spines an d axospinous synapses on hippocampal CA1 pyramidal cells in the adult female rat has been well-documented. However, presynaptic involvement in this process of synapse elimination and formation in the adult is u nknown. To address this issue, we have reconstructed 410 complete pres ynaptic boutons through coded serial electron micrographs of CA1 strat um radiatum to determine the: (1) frequency of multiple (MSB) vs. sing le (SSB) synapse boutons; (2) number of synaptic contacts per MSB; (3) bouton volume and surface area; and (4) types of spines in synaptic c ontact with MSBs and SSBs in ovariectomized, estradiol-treated animals (OVX + E) versus ovariectomized oil-treated controls (OVX + O). Quant itative analysis of this tissue revealed that, in OVX + E animals, 45. 0% of presynaptic boutons form multiple synaptic contacts with dendrit ic spines compared to 27.3% in controls (P <0.01); the average number of synapses per MSB was 2.7 in OVX + E animals compared to 2.3 in cont rols (P <0.05). This represents a 25.5% increase in the number of syna pses formed by a given number of presynaptic boutons in estradiol-trea ted animals (P <0.01) which largely accounts for the previously observ ed estradiol-induced increase in axospinous synapse density. There was no treatment effect on bouton size; however, because MSBs are larger than SSBs, the increased frequency of MSBs in estradiol-treated tissue results in a trend toward an estradiol-induced increase in average bo uton size. Additionally, MSBs were found to be more irregular in shape , i.e., significantly less spherical, than SSBs. Our results indicate that estradiol-induced dendritic spines form synapses primarily with p reexisting boutons in stratum radiatum and that these boutons enlarge and change shape as they accommodate new synapses. Such findings sugge st a relatively active role for dendrites in the process of adult syna pse formation. (C) 1996 Wiley-Liss, Inc.