ACTIVITY-DEPENDENT REGULATION OF NEU DIFFERENTIATION FACTOR NEUREGULIN EXPRESSION IN RAT-BRAIN

Neu differentiation factor (NDF/neuregulin) is widely expressed in the central and peripheral nervous systems, where it functions as a media tor of the interactions between nerve cells and Schwann, glia, oligode ndrocyte, and muscle cells, to control cellular proliferation, differe ntiation, and migration. NDF binds to two receptor tyrosine kinases, E rbB-3 and ErbB-4. Here we demonstrate that NDF and its ErbB-4 receptor are highly reactive to changes in ambient neuronal activity in the ro dent brain in a region-selective manner. Generation of epileptic seizu res by using kainic acid, a potent glutamate analog, elevated levels o f NDF transcripts in limbic cortical areas, hippocampus, and amygdala. Concomitantly, ErbB-4 mRNA nas increased with a similar spatial distr ibution, but transcription of the other NDF receptor, ErbB-3, did not change. A more moderate stimulation, forced locomotion, was accompanie d by an increase in NDF transcripts and protein in the hippocampus and in the motor cortex. Similar changes were found with ErbB-4, but not ErbB-3. Last, a pathway-specific tetanic stimulation of the perforant path, which produced long-term potentiation, was followed by induction of NDF expression in the ipsilateral dentate gyrus and CA3 area of th e hippocampus. Taken together, these results indicate that NDF is regu lated by physiological activity and may play a role in neural plastici ty.