Immediate Early Gene (IEG) Induction in the Basal Ganglia upon Electrical Stimulation of the Cerebral Cortex
The cerebral cortex is a major input to the basal ganglia through its topographically organized projections to the striatum and the subthalamic nucleus (STN). By the analysis of IEG (c-fos and zif268) mRNA expression, we found that unilateral stimulation of the cerebral cortex produced a bilateral induction of these IEG in limited striatal and subthalamic territories, which varied with the stimulated cortical area. In parallel to IEGs induction, peptide mRNAs encoding substance P and enkephalin, differentially expressed by the two efferent striatal neuronal populations, were also increased in the striatal territory activated by the cortical stimulation. The IEG induction involved the activation of ionotropic glutamate receptors (AMPA and NMDA). Among various intracellular signaling pathways that could be activated by these receptors, the Mitogen Activated Protein Kinase (MAPK) of the Extracellular Regulated-signal Kinase (ERK) subfamily, appeared to be predominant implicated in IEGs induction. In fact, the local injection of a specific inhibitor of the MAPK/ERK pathway (PD98059) totally abolished IEGmRNA upregulation. We conclude that this IEG induction could participate to adaptive mechanisms involved in long term synaptic plasticity in the basal ganglia.
Key wordsstriatum subthalamic nucleus c-Fos enkephalin subtance P zif 268 MKP1 CREB Elk-1 PD 98059 phosphorylation mRNA transcription
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