Role of activity-dependent BDNF expression in hippocampal-prefrontal cortical regulation of behavioral perseverance

Kazuko Sakata, Keri Martinowich, Newton H. Woo, Robert J. Schloesser, Dennisse V. Jimenez, Yuanyuan Ji, Liya Sheni, Bai Lu

Research output: Contribution to journalArticle

Abstract

Activity-dependent gene transcription, including that of the brain-derived neurotrophic factor (Bdnf) gene, has been implicated in various cognitive functions. We previously demonstrated that mutant mice with selective disruption of activity-dependent BDNF expression (BDNF-KIV mice) exhibit deficits in GABA-mediated inhibition in the prefrontal cortex (PFC). Here, we show that disruption of activity-dependent BDNF expression impairs BDNF-dependent late-phase long-term potentiation (L-LTP) in CA1, a site of hippocampal output to the PFC. Interestingly, early-phase LTP and conventional L-LTP induced by strong tetanic stimulation were completely normal in BDNF-KIV mice. In parallel, attenuation of activity-dependent BDNF expression significantly impairs spatial memory reversal and contextual memory extinction, two executive functions that require intact hippocampal-PFC circuitry. In contrast, spatial and contextual memory per se were not affected. Thus, activity-dependent BDNF expression in the hippocampus and PFC may contribute to cognitive and behavioral flexibility. These results suggest distinct roles for different forms of L-LTP and provide a link between activity-dependent BDNF expression and behavioral perseverance, a hallmark of several psychiatric disorders.

Original languageEnglish (US)
Pages (from-to)15103-15108
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number37
DOIs
StatePublished - Sep 10 2013

ASJC Scopus subject areas

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