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Registro de acceso cerrado CREB-dependent regulation of gad65 transcription by BDNF/TrκB in cortical interneurons

Autor :Sánchez-Huertas, Carlos
Rico, Beatriz
Fecha de publicación :2011
Editor:Oxford University Press
Citación :Cerebral Cortex 21(4): 777-788 (2011)
Resumen:In the cerebral cortex, the functional output of projection neurons is fine-tuned by inhibitory neurons present in the network, which use γ-aminobutyric acid (GABA) as their main neurotransmitter. Previous studies have suggested that the expression levels of the rate-limiting GABA synthetic enzyme, GAD65, depend on brain derived neurotrophic factor (BDNF)/TrκB activation. However, the molecular mechanisms by which this neurotrophic factor and its receptor controls GABA synthesis are still unknown. Here, we show a direct regulation of the GAD65 gene by BDNF-TrκB signaling via CREB in cortical interneurons. Conditional ablation of TrkB in cortical interneurons causes a cell-autonomous decrease in the synaptically enriched GAD65 protein and its transcripts levels, suggesting that transcriptional regulation of the GAD65 gene is altered. Dissection of the intracellular pathway that underlies this process revealed that BDNF/TrκB signaling controls the transcription of GAD65 in a Ras-ERK-CREB-dependent manner. Our study reveals a novel molecular mechanism through which BDNF/TrκB signaling may modulate the maturation and function of cortical inhibitory circuits. © 2011 The Author. Published by Oxford University Press. All rights reserved.
URI :http://hdl.handle.net/10261/53158
Identificadores:doi: 10.1093/cercor/bhq150
issn: 1047-3211
e-issn: 1460-2199
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