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


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.

SUBMITTER: Sakata K 

PROVIDER: S-EPMC3773762 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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

Sakata Kazuko K   Martinowich Keri K   Woo Newton H NH   Schloesser Robert J RJ   Jimenez Dennisse V DV   Ji Yuanyuan Y   Shen Liya L   Lu Bai B  

Proceedings of the National Academy of Sciences of the United States of America 20130826 37


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  ...[more]

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