Differential regulation of glutamate receptor-mediated BDNF mRNA expression in the cerebellum and its defects in stargazer mice

Activity-dependent regulation of BDNF expression plays important roles in synaptic plasticity and neuronal function. We have investigated glutamate receptor-mediated regulation of BDNF expression in the cerebellum of wild-type and stargazer (stg) mice. Both in vivo and in vitro studies revealed that BDNF response kinetics in the cerebellum were much delayed with reversed sensitivity to NMDA versus non-NMDA agonist exposures significantly different from those in the cortex and hippocampus of wild-type mice. In stg mice, the severely impaired BDNF expression was restricted to the cerebellum while responses in the forebrain were intact. A selective failure of BDNF mRNA response to AMPA stimulation, but not NMDA, was evident in cultured stg cerebellar granule cells. These results demonstrate that BDNF expression is differentially regulated with region-specific kinetics. It indicates that the BDNF expression defect in the stg cerebellum is attributable to the AMPA receptor defect caused by the stargazin mutation.