Essential role of brain-derived neurotrophic factor in adult hippocampal function.
Brain-derived neurotrophic factor (BDNF) regulates neuronal development and function. However, it has been difficult to discern its role in the adult brain in influencing complex behavior. Here, we use a recently developed inducible knockout system to show that deleting BDNF in broad forebrain regions of adult mice impairs hippocampal-dependent learning and long-term potentiation. We use the inducible nature of this system to show that the loss of BDNF during earlier stages of development causes hyperactivity and more pronounced hippocampal-dependent learning deficits. We also demonstrate that the loss of forebrain BDNF attenuates the actions of desipramine, an antidepressant, in the forced swim test, suggesting the involvement of BDNF in antidepressant efficacy. These results establish roles for BDNF in the adult, and demonstrate the strength of this inducible knockout system in studying gene function in the adult brain.
Monteggia
Lisa M
LM
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA. lisa.monteggia@utsouthwestern.edu
Barrot
Michel
M
Powell
Craig M
CM
Berton
Olivier
O
Galanis
Victor
V
Gemelli
Terry
T
Meuth
Sven
S
Nagy
Andreas
A
Greene
Robert W
RW
Nestler
Eric J
EJ
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003891:Desipramine / Q000378:metabolism; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017403:In Situ Hybridization; D007858:Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*
D000929:Antidepressive Agents, Tricyclic; D019208:Brain-Derived Neurotrophic Factor; D003891:Desipramine