ON THE ROLE OF C-FOS EXPRESSION IN STRIATAL TRANSMISSION - THE ANTISENSE OLIGONUCLEOTIDE APPROACH

The antisense oligonucleotide approach has been established as a tool to analyse the functional role of c-fos gene expression in the striatu m. Studies on the distribution and cellular localization of microinjec ted oligonucleotides, as well as their effect on gene expression, demo nstrate that the action of the c-fos oligonucleotides can be used to e valuate the role of c-fos gene expression selectively in neuronal func tion. Antisense oligonucleotides to c-fos inhibit both basal and stimu lated c-Sos expression in the striatum, which leads to characteristic changes in behavioural and biochemical parameters, as evaluated by ana lysis of rotational behaviour and dual probe in vivo microdialysis for the neurotransmitter GABA, respectively. These observations could be explained by a postulated D1/NMDA receptor interaction in the striaton igral GABA pathway controlled by the immediate early gene c-fos. We co ncluded that c-fos might be involved not only in the control of long-t erm changes in the cellular phenotype but also in control of firing ra te. (C) 1997 Elsevier Science Ltd.