GABA RELEASE AND GAD(67) MESSENGER-RNA EXPRESSION IN RAT HIPPOCAMPUS FOLLOWING ENTORHINAL CORTEX ACTIVATION

This study investigate the effect of stimulation of glutamatergic affe rents originating in the entorhinal cortex on possible changes of GABA ergic transmission in the CA1 subregion of the hippocampus. Microdialy sis was used to monitor extracellular GABA and in situ hybridization t o measure levels of glutamic acid decarboxylase(67) (GAD(67)) mRNA. A dose-dependent increase in extracellular levels of GABA in the dorsal CA1 subregion was detected following injection of 2.4 and 9.6 mu g qui squalate into the lateral entorhinal cortex whereas 0.24 mu g had no e ffect. The GABA increase was attenuated by local administration of tet rodotoxin (TTX), indicating neuronal origin, A 60% decrease and a 160% increase were seen in levels of GAD(67) mRNA in the CA1 following inj ection of 0.24 and 9.6 mu g quisqualate, respectively. This study prov ides evidence of an entorhinal cortex influenced stimulatory effect on GABAergic activity in the CA1. However, no direct relationship was fo und between stimulated GABA release and subsequently measured GAD(67) mRNA levels. The increased GABA release and the apparent adaptive incr ease in GAD(67) mRNA levels by the strongest stimulation may be due to an endogenous inhibitory neuroprotective response to an excitotoxic i nfluence. (C) 1997 Elsevier Science B.V.