LEARNING DEFICIT IN BDNF MUTANT MICE

Brain-derived neurotrophic factor (BDNF) has been implicated in the re gulation of high-frequency synaptic transmission and long-term potenti ation in the hippocampus, processes that are also thought to be involv ed in the learning of spatial tasks such as the Morris water maze. In order to determine whether BDNF is required for normal spatial learnin g, mice carrying a deletion in one copy of the BDNF gene were subjecte d to the Morris water maze task. Young adult BDNF mutant mice were sig nificantly impaired compared with wild-type mice, requiring twice the number of days to reach full performance. Aged wild-type mice performe d significantly worse than young wild-type mice and the effect was eve n more pronounced in the BDNF mutant mice, which did not learn at all. Although there was no difference in mean swimming speed between BDNF mutant and wild-type mice, we cannot exclude the possibility that deve lopmental or peripheral deficits also contribute to the learning defic its in these mice. In situ hybridization and RNase protection analysis revealed that BDNF mRNA expression was indeed decreased in BDNF mutan t mice. Furthermore, a pronounced effect of age on BDNF mRNA expressio n was seen, displayed as both a reduced level of mRNA expression and a reduced or entirely absent layer-specific expression pattern in the c erebral cortex of aged animals. Thus, our data suggest that BDNF expre ssion may be linked to learning.