Altered synaptic transmission in the hippocampus of the castrated male mouse is reversed by testosterone replacement.

Abstract

PURPOSE: To determine the effect of castration on hippocampal function, we have investigated synaptic transmission in the castrated male mouse in vivo. We also examined whether administering testosterone can reverse the changes. MATERIALS AND METHODS: Male 12 weeks-old C57BL/6J mice were divided into three experimental groups; sham-castration (Control), the castration group (Cast), and the castration plus testosterone propionate group (Cast+TP). Field excitatory postsynaptic potentials (fEPSP) were evoked in the CA1 area of the hippocampus by stimulating the commissural fibers of the contralateral hippocampus. Field EPSPs were evoked in the granular cells of the dentate gyrus (DG) by stimulating the ipsilateral perforant path fibers. RESULTS: Laminar analysis of the fEPSPs in the hippocampal CA1 pyramidal cell layer did not differ significantly between the three experimental groups. However, paired pulse facilitation (PPF) of the fEPSP with short inter-stimulus intervals (30 to 100 msec) was significantly suppressed in Cast group. This suppression was reversed by testosterone injection (Cast+TP). Longterm potentiation (LTP) in the CA1 pyramidal neurons by high frequency stimulation (HFS) did not differ significantly between the three experimental groups, whereas potentiation evoked by primed burst stimulation (PBS) was much weaker in the Cast group compared with the Control group. Testosterone injection restored the PBS-induced potentiation to the control level. Synaptic transmission between perforant pathway and the granule cells in the dentate gyrus (DG) did not differ significantly among the three experimental groups. CONCLUSIONS: Suppression of PPF and impairment of the potentiation by PBS in CA1 hippocampal neurons was observed in castrated male mice and these changes were reversed by testosterone injection. These findings suggest that altered synaptic transmission in the castrated male mouse is caused by disturbance of inhibitory neuronal networks that are influenced by testosterone.