THE INVOLVEMENT OF BRAIN-DERIVED NEUROTROPHIC FACTOR IN HIPPOCAMPAL LONG-TERM POTENTIATION REVEALED BY GENE TARGETING EXPERIMENTS

Brain-derived neurotrophic factor (BDNF) is a member of the NGF gene f amily, which has been shown to influence the survival and differentiat ion of specific classes of neurons in vitro and in vivo. The possibili ty that neurotrophins are also involved in processes of neuronal plast icity has only recently begun to receive attention. To determine wheth er BDNF has a function in processes like long-term potentiation (LTP), we produced a strain of mice with a deletion in the coding sequence o f the BDNF-gene. We then used hippocampal slices from these mice to in vestigate whether LTP is affected by this mutation. Mutant mice showed significantly weaker LTP in the CA1 region. The magnitude of the pote ntiation as well as the percentage of cases in which LTP could be indu ced successfully was clearly reduced whereas important pharmacological and morphological control parameters in the hippocampus of these anim als were unaffected. Adenoviral vectors were used to re-express BDNF i n acute slices of BDNF-knock-out mice. Inmost cases LTP could be rescu ed with this approach. These results suggest that BDNF has an importan t functional role in the expression of LTP in the hippocampus.