A role for monomeric G-proteins in synaptic plasticity in the rat dentate gyrus in vitro

Recent studies have implicated Ras signalling in synaptic plasticity. In this study we have investigated a role for the low molecular weight G proteins Ras, Rap, Ra1 and Rac in long-term potentiation and depression using Clostridium Sordelli Lethal Toxin-82 (LT-82), which inactivates Ras, Rap, Ra1 and Rac, and manumycin A, a Ras inhibitor. Perfusion of hippocampal slices with LT-82 (200 ng/ml) attenuated LTP (83+/-10%, n=5, P<0.01, compared with controls of 160+/-11% at 60 min post HFS, n=5). LT-82 had no effect on LTD (63+/-1% at 100 ng/ml, n=5 and 66+/-1% at 200 ng/ml, n=4, compared to controls of 56+/-6%, n=6). Manumycin A (2 microM) had no effect on LTP (162+/-2%, n=5, compared to controls of 167+/-13%, n=5), but significantly attenuated LTD (88+/-6%, n=5, P<0.01, compared to controls of 63+/-9%, n=7). LT-82 (200 ng/ml) significantly increased the amplitude of the isolated NMDA-EPSP at 60 min post-drug application (240+/-40%, n=5, P<0.01, compared with controls of 100+/-4%, n=5). However, manumycin A, had no significant effect on NMDAR-EPSP amplitude (92+/-2%, n=5, compared with controls). These results demonstrate an important role for Ras in LTD and a role for Rap, Ra1 and Rac in LTP.