Role of pertussis toxin-sensitive G-proteins in synaptic transmission and plasticity at corticostriatal synapses

The role of pertussis toxin (PTX)-sensitive G-proteins in corticostriatal s ynaptic transmission and long-term synaptic depression (LTD) was examined u sing extracellular field potential and whole cell voltage-clamp recordings in striatal slices. High-frequency stimulation (HFS) produced LTD, defined as long-lasting decreases both in synaptically driven population spikes (PS s) measured with field potential recording and in excitatory postsynaptic c urrents (EPSCs) measured with whole cell recording. Striatal LTD could not be induced in slices obtained from rats that had received a unilateral intr astriatal injection of PTX. However, LTD could be induced in slices obtaine d from paired control slices. Furthermore, striatal LTD was prevented by pr etreat ment with N-ethylmaleimide (NEM), another compound that disrupts the function of PTX-sensitive G-proteins. NEM? itself, also potentiated PS and EPSC amplitudes. In addition, NEM increased the frequency and amplitude of both spontaneous and miniature EPSCs and decreased the paired-pulse facili tation ratio, suggesting that it may act on both pre- and postsynaptic site s. The findings suggest that PTX-sensitive G-proteins have multiple roles a t corticostriatal synapses, including regulation of synaptic transmission a t both pre- and postsynaptic sites, and a key role in striatal LTD.