Coincident stimulation of convergent cortical inputs enhances immediate early gene induction in the striatum

The effect of coincident stimulation of convergent corticostriatal inputs was analyzed by the induction of immediate early genes in striatal neurons. Cortical motor areas were stimulated through implanted electrodes in awake, behaving rats, and the induction of the mRNAs encoding the immediate early genes (IEGs) c-fos and arc was analyzed in the striatum with in situ hybridization histochemistry. In the first experiment, unilateral stimulation of the medial agranular cortex, orofacial region of the lateral agranular cortex or the forelimb region of the lateral agranular cortex resulted in IEG induction in the striatum, which was restricted to the topographically related area receiving input from the stimulated cortical area. In a second experiment, stimulation parameters were altered, including frequency, number of pulses/train, and number of trains/s. These parameters did not have a significant effect on IEG induction. Notably, in some cases, in which there was IEG induction not only in the stimulated cortical region, but also in the homologous area in the contralateral hemisphere, very robust IEG induction was observed in the striatum. In a third experiment, the orofacial regions of the lateral agranular cortex of both hemispheres were stimulated coincidently. All of these animals showed robust striatal IEG induction. This IEG induction was attenuated by pretreatment with an NMDA antagonist MK-801. In a fourth experiment, we tested whether the coincidence of bilateral cortical stimulation contributed to the efficacy of striatal IEG induction. Either alternating stimulation or coincident stimulation of non-homologous cortical regions produced significantly lower striatal IEG induction than obtained with coincident stimulation of homologous cortical areas. Enhanced striatal IEG induction occurred in indirect striatal neurons, labeled with enkephalin, but was also present in a large number of enkephalin-negative neurons, most of which are likely direct pathway neurons. These results suggest that regional and temporal convergence of cortical inputs enhances striatal IEG induction.