IMPAIRED EYE-BLINK CONDITIONING IN WAGGLER, A MUTANT MOUSE WITH CEREBELLAR BDNF DEFICIENCY

In addition to their trophic functions, neurotrophins are also implica ted in synaptic modulation and learning and memory. Although gene knoc kout techniques have been used widely in studying the roles of neurotr ophins at molecular and cellular levels, behavioral studies using neur otrophin knockouts are limited by the early-onset lethality and variou s sensory deficits associated with the gene knockout mice. In the pres ent study, we found that in a spontaneous mutant mouse, waggler, the e xpression of brain-derived neurotrophic factor (BDNF) was selectively absent in the cerebellar granule cells. The cytoarchitecture of the wa ggler cerebellum appeared to be normal at the light microscope level. The mutant mice exhibited no sensory deficits to auditory stimuli or h eat-induced pain. However, they were massively impaired in classic eye -blink conditioning. These results suggest that BDNF may have a role i n normal cerebellar neuronal function, which, in turn, is essential fo r classic eye-blink conditioning.