Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex

Kazuko Sakata, Newton H. Woo, Keri Martinowich, Joshua S. Greene, Robert J. Schloesser, Liya Shen, Bai Lu

Research output: Contribution to journalArticle

121 Citations (Scopus)

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 activitydependent 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.

Original languageEnglish (US)
Pages (from-to)5942-5947
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number14
DOIs
StatePublished - Apr 7 2009

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Neuronal Plasticity
Brain-Derived Neurotrophic Factor
Prefrontal Cortex
Parvalbumins
Pyramidal Cells
Executive Function
Interneurons
Synaptic Transmission
Exons
Schizophrenia
Proteins

All Science Journal Classification (ASJC) codes

  • General

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Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex. / Sakata, Kazuko; Woo, Newton H.; Martinowich, Keri; Greene, Joshua S.; Schloesser, Robert J.; Shen, Liya; Lu, Bai.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 14, 07.04.2009, p. 5942-5947.

Research output: Contribution to journalArticle

Sakata, Kazuko ; Woo, Newton H. ; Martinowich, Keri ; Greene, Joshua S. ; Schloesser, Robert J. ; Shen, Liya ; Lu, Bai. / Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 14. pp. 5942-5947.
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