PMID- 19293383 OWN - NLM STAT- MEDLINE DCOM- 20090506 LR - 20220321 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 106 IP - 14 DP - 2009 Apr 7 TI - Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex. PG - 5942-7 LID - 10.1073/pnas.0811431106 [doi] AB - 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. FAU - Sakata, Kazuko AU - Sakata K AD - 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. FAU - Woo, Newton H AU - Woo NH FAU - Martinowich, Keri AU - Martinowich K FAU - Greene, Joshua S AU - Greene JS FAU - Schloesser, Robert J AU - Schloesser RJ FAU - Shen, Liya AU - Shen L FAU - Lu, Bai AU - Lu B LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20090317 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics MH - Excitatory Postsynaptic Potentials MH - Inhibitory Postsynaptic Potentials MH - Mice MH - Mice, Mutant Strains MH - Prefrontal Cortex/*physiology MH - Promoter Regions, Genetic/*physiology MH - Synaptic Potentials MH - *Synaptic Transmission MH - *Transcription, Genetic PMC - PMC2667049 COIS- The authors declare no conflict of interest. EDAT- 2009/03/19 09:00 MHDA- 2009/05/07 09:00 PMCR- 2009/10/07 CRDT- 2009/03/19 09:00 PHST- 2009/03/19 09:00 [entrez] PHST- 2009/03/19 09:00 [pubmed] PHST- 2009/05/07 09:00 [medline] PHST- 2009/10/07 00:00 [pmc-release] AID - 0811431106 [pii] AID - 7127 [pii] AID - 10.1073/pnas.0811431106 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5942-7. doi: 10.1073/pnas.0811431106. Epub 2009 Mar 17.