Essential role of brain-derived neurotrophic factor in adult hippocampal function

Lisa M Monteggia, Michel Barrot, Craig M Powell, Olivier Berton, Victor Galanis, Terry Gemelli, Sven Meuth, Andreas Nagy, Robert Greene, Eric J. Nestler

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501 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10827-10832
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number29
DOIs
StatePublished - Jul 20 2004

ASJC Scopus subject areas

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    Monteggia, L. M., Barrot, M., Powell, C. M., Berton, O., Galanis, V., Gemelli, T., Meuth, S., Nagy, A., Greene, R., & Nestler, E. J. (2004). Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proceedings of the National Academy of Sciences of the United States of America, 101(29), 10827-10832. https://doi.org/10.1073/pnas.0402141101