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The Journal of Neuroscience, May 27, 2009, 29(21):7040-7052; doi:10.1523/JNEUROSCI.0105-09.2009

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Development/Plasticity/Repair
Transcriptional and Electrophysiological Maturation of Neocortical Fast-Spiking GABAergic Interneurons

Benjamin W. Okaty, ^* Mark N. Miller, ^* Ken Sugino, Chris M. Hempel, and Sacha B. Nelson

Department of Biology, Brandeis University, Waltham, Massachusetts 02453

Correspondence should be addressed to Sacha B. Nelson, Biology Department, MS-008, Brandeis University, 415 South Street, Waltham, MA 02453. Email: nelson{at}brandeis.edu

Fast-spiking (FS) interneurons are important elements of neocortical circuitry that constitute the primary source of synaptic inhibition in adult cortex and impart temporal organization on ongoing cortical activity. The highly specialized intrinsic membrane and firing properties that allow cortical FS interneurons to perform these functions are attributable to equally specialized gene expression, which is ultimately coordinated by cell-type-specific transcriptional regulation. Although embryonic transcriptional events govern the initial steps of cell-type specification in most cortical interneurons, including FS cells, the electrophysiological properties that distinguish adult cortical cell types emerge relatively late in postnatal development, and the transcriptional events that drive this maturational process are not known. To address this, we used mouse whole-genome microarrays and whole-cell patch clamp to characterize the transcriptional and electrophysiological maturation of cortical FS interneurons between postnatal day 7 (P7) and P40. We found that the intrinsic and synaptic physiology of FS cells undergoes profound regulation over the first 4 postnatal weeks and that these changes are correlated with primarily monotonic but bidirectional transcriptional regulation of thousands of genes belonging to multiple functional classes. Using our microarray screen as a guide, we discovered that upregulation of two-pore K⁺ leak channels between P10 and P25 contributes to one of the major differences between the intrinsic membrane properties of immature and adult FS cells and found a number of other candidate genes that likely confer cell-type specificity on mature FS cells.

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Received Jan. 8, 2009; revised March 17, 2009; accepted April 21, 2009.

Correspondence should be addressed to Sacha B. Nelson, Biology Department, MS-008, Brandeis University, 415 South Street, Waltham, MA 02453. Email: nelson{at}brandeis.edu

This article has been cited by other articles:

				D. L. Jones and S. C. Baraban Inhibitory Inputs to Hippocampal Interneurons Are Reorganized in Lis1 Mutant Mice J Neurophysiol, August 1, 2009; 102(2): 648 - 658. [Abstract] [Full Text] [PDF]

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