The Effect And Mechanism Of Pregnenolone Sulfate On Evoked Excitatory Synaptic Transmission In Rat Prelimbic Cortical Neurons

Pregnenolone sulfate (PREGS) is one of the most abundantly produced neurosteroids in the brain. Plentiful of experiments suggest that pregnenolone sulfate has significant effect on cognition, but the mechanism is not clear now. Prelimbic cortex is the the main brain region for cognition, and the excitatory synaptic transmission in the pyramidal cells of the prelimbic cortex is crucial for its physiological function. So, pregnenolone sulfate might have effect on this excitatory synaptic transmission, but this hypothesis need to be determined by experiment.The present paper studies the effect and its mechanism of pregnenolone sulfate on excitatory synaptic transmission in the pyramidal cells of the layer V-VI of the prelimbic cortex using whole-cell patch-clamp with electric stimulus and pharmacological methods in slices. We found that pregnenolone sulfate inhibited stimulus-evoked excitatory postsynaptic currents (EPSC); the effect of pregnenolone sulfate was significant at concentration of 1 μM and increased with an increase in concentrations; the time course showed that the effect of pregnenolone sulfate began to appear at 5 min, persisted throughout the rest of the experiment and was irreversible during washout.To determine the position of its effect, we studied the effect of pregnenolone sulfate on the amplitude and frequency of miniature excitatory spontaneous postsynaptic currents, the amplitude of AMPA evoked current, the paired-pulse facilitation and dopamine and 5-HT-evoked increase in the frequency of spontaneous excitatory postsynaptic currents. We found that pregnenolone sulfate had no effects on the amplitude and frequency of miniature excitatory spontaneous postsynaptic currents, but significantly enhanced the paired-pulse facilitation (PPF) and inhibited dopamine and 5-HT-evoked increase in the frequency of spontaneous excitatory postsynaptic currents, these results indicated pregnenolone sulfate inhibited EPSC by presynaptic but not postsynaptic function.It's interesting that pregnenolone sulfate inhibited the electric stimulus, dopamine and 5-HT-evoked presynaptic glutamate release, but had no effect on the frequency of spontaneous excitatory postsynaptic currents, this result indicated that pregnenolone sulfate inhibit the evoked presynaptic glutamate release selectively. To elucidate the mechanism of the inhibition effect of pregnenolone sulfate on the evoked presynaptic...