Maintenance of muscimol-induced long-term depression by neurosteroids

1. The present study was undertaken to expand investigations of the interaction between neurosteroids and long-term depression (LTD) induced by muscimol 10 mu M. 2. Extracellular recordings were made in the CAl pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). 3. As previously reported, muscimol at 10 mu M induced a time, frequency of stimulation and concentration-dependent LTD of amplitude of orthodromic potentials. Alphaxalone, at concentrations that had no significant effect themselves on the population spike (0.5 and 1 mu M), potentiated the inhibitory effect of muscimol on the population spike size. 4. It is now reported that low concentrations of alphaxalone are able to potentiate the ability of muscimol to induce LTD. In addition, concentrations of muscimol as low as 1 mu M which are not themselves able to induce LTD, as well as alphaxalone and 5 alpha-pregnan-3 alpha-ol-20-one 1 mu M were able to maintain the LTD induced by muscimol 10 mu M. 5. It is suggested that the ability of such low concentrations of GABA receptor agonists to maintain LTD could be of physiological importance.