Abstract
The neurosteroid dehydroepiandrosterone sulfate (DHEAS) is known to improve memory and learning, however, little is known about the underlying synaptic mechanism. We examined the effects of chronic administration of DHEAS (20mg/kg for 7 days) on the plasticity of Schaffer collateral-CA1 synapse using an optical recording technique on rat hippocampal slices stained with a voltage-sensitive dye. DHEAS significantly facilitated the induction of frequency-dependent LTP. While tetanus of at least 50 pulses (at 100 Hz) was required to induce LTP in control rats, only 20 pulses were needed in DHEAS-treated animals. DHEAS did not alter the presynaptic glutamate release. Co-administration of the sigma 1 receptor antagonist NE100 with DHEAS perfectly inhibited the DHEAS-facilitated LTP. In slices from the DHEAS-treated rats, the NMDA-induced intracellular Ca2+ ([Ca2+]i) increase in CA1 pyramidal neurons was significantly potentiated. The sub-threshold tetanus markedly increased the tyrosine phosphorylation of Src in the DHEAS-treated rats, which critically depended on the potentiated [Ca2+]i increase. Conversely, the Src family kinase inhibitor PP2 attenuated the NMDA-induced [Ca2+]i increase and abolished the DHEAS-facilitated LTP, suggesting that the potentiated NMDAR function and Src activation are interdependent. This novel postsynaptic NMDAR-mediated signal amplification through [NMDAR/Ca2+-Src-NMDAR/Ca2+] cycle may play a pivotal role in the DHEAS-facilitated LTP induction. [J Physiol Sci. 2008;58 Suppl:S121]
