LOCAL RELEASE OF GABAERGIC INHIBITION IN THE MOTOR CORTEX INDUCES IMMEDIATE-EARLY GENE-EXPRESSION IN INDIRECT PATHWAY NEURONS OF THE STRIATUM

The neocortex is thought to exert a powerful influence over the functi ons of the basal ganglia via its projection to the striatum. It is not known, however, whether corticostriatal effects are similar across di fferent types of striatal projection neurons and interneurons or are u nique for cells having different functions within striatal networks. T o examine this question, we developed a method for focal synchronous a ctivation of the primary motor cortex (MI) of freely moving rats by lo cal release of GABAergic inhibition. With this method, we monitored co rtically evoked activation of two immediate-early gene protein product s, c-Fos and JunB, in phenotypically identified striatal neurons. We f urther studied the influence of glutamate receptor antagonists on the stimulated expression of c-Fos, JunB, FosB, and NGFI-A. Local disinhib ition of MI elicited remarkably selective induction of c-Fos and JunB in enkephalinergic projection neurons. These indirect pathway neurons, through their projections to the globus pallidus, can inhibit thalamo cortical motor circuits. The dynorphin-containing projection neurons o f the direct pathway, with opposite effects on the thalamocortical cir cuits, showed very little induction of c-Fos or JunB, The gene respons e of striatal interneurons was also highly selective, affecting princi pally parvalbumin- and NADPH diaphorase-expressing interneurons. The g lutamate NMDA receptor antagonist MK-801 strongly reduced the cortical ly evoked striatal gene expression in all cell types for each gene exa mined. Because the gene induction that we found followed known cortico striatal somatotopy, was dose-dependent, and was selectively sensitive to glutamate receptor antagonists, we suggest that the differential a ctivation patterns reflect functional specialization of cortical input s to the direct and indirect pathways of the basal ganglia and functio nal plasticity within these circuits.