Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex.
Proc Natl Acad Sci U S A
; 106(14): 5942-7, 2009 Apr 07.
Article
em En
| MEDLINE
| ID: mdl-19293383
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Regiões Promotoras Genéticas
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Córtex Pré-Frontal
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Transmissão Sináptica
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Fator Neurotrófico Derivado do Encéfalo
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos