CEREBELLAR BRAIN-DERIVED NEUROTROPHIC FACTOR-TRKB DEFECT ASSOCIATED WITH IMPAIRMENT OF EYEBLINK CONDITIONING IN STARGAZER MUTANT MICE

In the spontaneous ataxic mutant mouse stargazer, there is a selective reduction of brain-derived neurotrophic factor (BDNF) mRNA expression in the cerebellum. BDNF protein levels in the cerebellum are reduced by 70%. Despite normal levels of full length and truncated TrkB recept or, constitutive and neurotrophin-4/5-induced tyrosine phosphorylation was significantly reduced in several signal transduction molecules, i ncluding phospholipase-C gamma 1, erk1, and erk2. Morphological examin ation revealed an increased number of external granule cells at postna tal day 15 and the presence of abnormal neurons resembling immature gr anule cells in the adult. These abnormalities are associated with a se vere impairment in the acquisition of classical eyeblink conditioning, indicating cerebellar malfunction. Our data suggest that normal BDNF expression and TrkB signal transduction in the cerebellum are necessar y for learning and plasticity in this model.