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A Biological Function for the Neuronal Activity-Dependent Component of Bdnf Transcription in the Development of Cortical Inhibition

Hong, Elizabeth J. and McCord, Alejandra E. and Greenberg, Michael E. (2008) A Biological Function for the Neuronal Activity-Dependent Component of Bdnf Transcription in the Development of Cortical Inhibition. Neuron, 60 (4). pp. 610-624. ISSN 0896-6273. PMCID PMC2873221. doi:10.1016/j.neuron.2008.09.024.

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Neuronal activity-regulated gene expression has been suggested to be an important mediator of long-lasting, experience-dependent changes in the nervous system, but the activity-dependent component of gene transcription has never been selectively isolated and tested for its functional significance. Here, we demonstrate that introduction of a subtle knockin mutation into the mouse Bdnf gene that blocks the ability of the activity-regulated factor CREB to bind Bdnf promoter IV results in an animal in which the sensory experience-dependent induction of Bdnf expression is disrupted in the cortex. Neurons from these animals form fewer inhibitory synapses, have fewer spontaneous inhibitory quantal events, and exhibit reduced expression of inhibitory presynaptic markers in the cortex. These results indicate a specific requirement for activity-dependent Bdnf expression in the development of inhibition in the cortex and demonstrate that the activation of gene expression in response to experience-driven neuronal activity has important biological consequences in the nervous system.

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Additional Information:© 2008 Elsevier. Accepted: September 12, 2008. Published: November 25, 2008. We thank A.E. West for stimulating discussions and guidance in the conceptual design of this study; P.L. Greer, A.E. West, J. Zieg, and E.C. Griffith for critical readings of the manuscript; M. Gee for assistance with mouse colony management; B.L. Bloodgood and C. Chen for technical consultations about electrophysiological recordings and analysis; C. Chen and M. Fagiolini for the use of their dark-rearing facilities; the MRDDRC Gene Manipulation Core (M. Thompson, Y. Zhou, and H. Ye); the MRDDRC Imaging Core (L. Bu); and the MRDDRC Histology Core (M. Liana). M.E.G. acknowledges the generous support of the F.M. Kirby Foundation to the Neurobiology Program at Children's Hospital. This work was supported by a John and Fannie Hertz Foundation fellowship to E.J.H., NIH grant R01-NS-048276 to M.E.G., and MRDDRC grant NIH-P30-HD-18655.
Funding AgencyGrant Number
F. M. Kirby FoundationUNSPECIFIED
Fannie and John Hertz FoundationUNSPECIFIED
Subject Keywords:CELLBIO; MOLNEURO
Issue or Number:4
PubMed Central ID:PMC2873221
Record Number:CaltechAUTHORS:20151005-161441116
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Official Citation:Elizabeth J. Hong, Alejandra E. McCord, Michael E. Greenberg, A Biological Function for the Neuronal Activity-Dependent Component of Bdnf Transcription in the Development of Cortical Inhibition, Neuron, Volume 60, Issue 4, 26 November 2008, Pages 610-624, ISSN 0896-6273, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:60786
Deposited By: George Porter
Deposited On:06 Oct 2015 21:24
Last Modified:10 Nov 2021 22:39

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