Abstract
We used high-speed optical recordings to study the effect of PREGS, one of the most important neurosteroids, on glutamate releases in rat hippocampal slices stained with the voltage-sensitive dye RH-155. PREGS acutely and dose-dependently enhanced the propagation of neuronal excitation in the dentate gyrus by augmenting the EPSP in granule cells. PREGS enhanced paired-pulse facilitation (PPF), a parameter reflecting changes in the properties of presynaptic terminals, suggesting that the augmented EPSP arises from the increased glutamate releases. To test this hypothesis we measured synaptically-induced glial depolarization (SIGD) that is an indicative of the glutamate transporter activity representing the amount of presynaptic glutamate releases. PREGS increased the amplitude and duration of SIGD, strongly supporting the idea that PREGS enhanced glutamate releases. The PREGS-effect on SIGD was prevented by the selective α7nAChR antagonists, α-BGT and MLA. Moreover GTS-21, a selective α7nAChR agonist, mimicked the PREGS-effect on SIGD and antagonized the effect of PREGS. The magnitude of the PREGS effect depended on external Ca2+ concentration and was attenuated by the blockade of L-type Ca channel. Taken together we propose a novel mechanism of the PREGS effect that the drug sensitizes presynaptic α7nAChR followed by an activation of L-type Ca channels to increase glutamate releases. [Jpn J Physiol 54 Suppl:S149 (2004)]
