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 family, which has been shown to influence the survival and differentiation of specific classes of neurons in vitro and in vivo. The possibility that neurotrophins are also involved in processes of neuronal plasticity has only recently begun to receive attention. To determine whether BDNF has a function in processes like long-term potentiation (LTP), we produced a strain of mice with a deletion in the coding sequence of the BDNF-gene. We then used hippocampal slices from these mice to investigate whether LTP is affected by this mutation. Mutant mice showed significantly weaker LTP in the CA1 region. The magnitude of the potentiation as well as the percentage of cases in which LTP could be induced successfully was clearly reduced whereas important pharmacological and morphological control parameters in the hippocampus of these animals were unaffected. Adenoviral vectors were used to re-express BDNF in acute slices of BDNF-knock-out mice. In most cases LTP could be rescued with this approach. These results suggest that BDNF has an important functional role in the expression of LTP in the hippocampus.
Korte
M
M
Max-Planck Institut für Psychiatrie, München-Martinsried, Germany.
Staiger
V
V
Griesbeck
O
O
Thoenen
H
H
Bonhoeffer
T
T
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D017921:Mastadenovirus / Q000235:genetics; D051379:Mice; D008818:Mice, Neurologic Mutants; D005810:Multigene Family; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009414:Nerve Growth Factors