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

Abstract

The role of pertussis toxin (PTX)-sensitive G-proteins in corticostriatal synaptic transmission and long-term synaptic depression (LTD) was examined using 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 (PSs) measured with field potential recording and in excitatory postsynaptic currents (EPSCs) measured with whole cell recording. Striatal LTD could not be induced in slices obtained from rats that had received a unilateral intrastriatal injection of PTX. However, LTD could be induced in slices obtained from paired control slices. Furthermore, striatal LTD was prevented by pretreatment 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 facilitation ratio, suggesting that it may act on both pre- and postsynaptic sites. The findings suggest that PTX-sensitive G-proteins have multiple roles at corticostriatal synapses, including regulation of synaptic transmission at both pre- and postsynaptic sites, and a key role in striatal LTD.