Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex.
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.
Sakata
Kazuko
K
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.
Woo
Newton H
NH
Martinowich
Keri
K
Greene
Joshua S
JS
Schloesser
Robert J
RJ
Shen
Liya
L
Lu
Bai
B
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
D019208:Brain-Derived Neurotrophic Factor