title: 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.
authors: Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, Genes, Cognition and Psychosis Program, Laboratory of Molecular Pathophysiology, National Institute of Mental Health, and National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors: Kazuko
authors: K
authors: Sakata
authors: Keri
authors: K
authors: Martinowich
authors: Newton H
authors: NH
authors: Woo
authors: Robert J
authors: RJ
authors: Schloesser
authors: Dennisse V
authors: DV
authors: Jimenez
authors: Yuanyuan
authors: Y
authors: Ji
authors: Liya
authors: L
authors: Shen
authors: Bai
authors: B
authors: Lu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D003071:Cognition / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology; D015870:Gene Expression; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D017397:Prefrontal Cortex / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
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