Neurosteroids exhibit differential effects on mIPSCs recorded from normal and seizure prone rats.

In the perirhinal cortex of seizure prone (SP) rats, GABA(A)-mediated miniature inhibitory postsynaptic currents (mIPSCs) are smaller in amplitude but have longer deactivation phases than mIPSCs recorded in normal control (NC; outbred) rats. These differences in mIPSCs are correlated to the relatively higher alpha1 subunit expression in the NC rat strains and the higher alpha2, alpha3, and alpha5 subunit expression in the SP strain. Using patch-clamp recording, we investigated how the neurosteroids tetrahydrodeoxcorticosterone (THDOC) and allopregnanolone at physiological and pharmacological concentrations may differentially affect the mIPSCs in the perirhinal cortex of brain slices isolated from SP and NC rats. We found that 100 nM THDOC prolonged the time course and increased the amplitude of both the mono- and biphasic mIPSCs in the SP rats, but these effects were smaller in the NC rats. By comparison, allopregnanolone (100 nM) had small effects in both the NC and SP rats. At 1.0 microM, THDOC enhanced mIPSCs in both strains, but this effect was not greater in the SP rat than it was at 100 nM. By contrast, allopregnanolone (500 nM) enhanced the time course of the mIPSCs in both strains but it reduced mIPSC amplitudes as well. THDOC (100 nM) was much more effective than 100 nM allopregnanolone in inducing a tonic current in SP and NC rats. These data show that neurosteroids modulate synaptic activity at synapses having different biophysical behaviors. As differing GABA(A) receptors are targeted by subsets of interneurons, these data suggest these neurosteroids may selectively modulate one inhibitory input over another.