Gender differences in human cortical synaptic density

Abstract

Certain cognitive functions differ in men and women, although the anatomical and functional substrates underlying these differences remain unknown. Because neocortical activity is directly related with higher brain function, numerous studies have focused on the cerebral cortex when searching for possible structural correlates of cognitive gender differences. However, there are no studies on possible gender differences at the synaptic level. In the present work we have used stereological and correlative light and electron microscopy to show that men have a significantly higher synaptic density than women in all cortical layers of the temporal neocortex. These differences may represent a microanatomical substrate contributing to the functional gender differences in brain activity.

Fig. 1.

Graphs of the neuronal densities, volume fraction (V_v), synaptic densities, and synapses per neurons in men and women in each cortical layer. (A) Graph showing the neuronal densities (mean ± SEM) in each cortical layer demonstrating that there are no significant differences between men and women. (B) Comparison of the V_v between men and women, calculated for the neuropil, cell bodies (including those from glia and neurons), and blood vessels in each cortical layer. Note that the neuropil represents between 90% and 98% of the volume, for which no significant differences were found between men and women. (C) Graph showing a comparison of synaptic density (mean ± SEM) between men and women in each cortical layer. w, women; m, men. *, P < 0.05; **, P < 0.01.

Fig. 2.

Electron micrographs to illustrate the ultrastructure of the human temporal neocortex. (A and B) Low-power electron micrographs showing the neuropil from layer IIIb of the temporal neocortex from a woman (A) and a man (B). Some synapses are indicated by arrows, and the asterisks illustrate two dendritic spines that are also shown at higher magnification in Fig. S3. (C and D) High-power electron micrographs showing the two major morphological types of synapses in the neuropil. Asymmetric synapses (arrows) had a prominent postsynaptic density, whereas symmetric synapses (arrowhead) had a thin postsynaptic density. de, dendritic shaft; ds, dendritic spines; T, axon terminals. [Scale bar (in D): 0.9 μm for A and B and 0.4 μm for C and D.]