title: Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex.
abstract: Transcription of Bdnf is controlled by multiple promoters, which drive expression of multiple transcripts encoding for the same protein. Promoter IV contributes significantly to activity-dependent brain-derived neurotrophic factor (BDNF) transcription. We have generated promoter IV mutant mice (BDNF-KIV) by inserting a GFP-STOP cassette within the Bdnf exon IV locus. This genetic manipulation results in disruption of promoter IV-mediated Bdnf expression. BDNF-KIV animals exhibited significant deficits in GABAergic interneurons in the prefrontal cortex (PFC), particularly those expressing parvalbumin, a subtype implicated in executive function and schizophrenia. Moreover, disruption of promoter IV-driven Bdnf transcription impaired inhibitory but not excitatory synaptic transmission recorded from layer V pyramidal neurons in the PFC. The attenuation of GABAergic inputs resulted in an aberrant appearance of spike-timing-dependent synaptic potentiation (STDP) in PFC slices derived from BDNF-KIV, but not wild-type littermates. These results demonstrate the importance of promoter IV-dependent Bdnf transcription in GABAergic function and reveal an unexpected regulation of STDP in the PFC by BDNF.
authors.affiliation: Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, National Institutes of Health, 35 Lincoln Drive, Bethesda, MD 20892-3714, USA.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Sakata
authors.forename: Newton H
authors.initials: NH
authors.lastname: Woo
authors.forename: Keri
authors.initials: K
authors.lastname: Martinowich
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Greene
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schloesser
authors.forename: Liya
authors.initials: L
authors.lastname: Shen
authors.forename: Bai
authors.initials: B
authors.lastname: Lu
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D019706:Excitatory Postsynaptic Potentials; D053444:Inhibitory Postsynaptic Potentials; D051379:Mice; D008817:Mice, Mutant Strains; D017397:Prefrontal Cortex / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D055366:Synaptic Potentials; D009435:Synaptic Transmission; D014158:Transcription, Genetic
chemical_list: D019208:Brain-Derived Neurotrophic Factor