Document Detail

Transcriptional and electrophysiological maturation of neocortical fast-spiking GABAergic interneurons.
MedLine Citation:
PMID:  19474331     Owner:  NLM     Status:  MEDLINE    
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.
Benjamin W Okaty; Mark N Miller; Ken Sugino; Chris M Hempel; Sacha B Nelson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  29     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-28     Completed Date:  2009-06-23     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7040-52     Citation Subset:  IM    
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MeSH Terms
Action Potentials / drug effects,  physiology*
Age Factors
Analysis of Variance
Animals, Newborn
Electric Stimulation
Excitatory Amino Acid Antagonists / pharmacology
Flow Cytometry / methods
Gene Expression Regulation, Developmental / drug effects,  physiology
Gene Regulatory Networks / drug effects,  physiology*
Glutamate Decarboxylase / genetics
Green Fluorescent Proteins / genetics
Inhibitory Postsynaptic Potentials / drug effects,  genetics
Interneurons / classification,  drug effects,  physiology*
Ion Channels / genetics,  metabolism
Lysine / analogs & derivatives,  metabolism
Mice, Transgenic
Microarray Analysis / methods
Neocortex / cytology*,  growth & development*
Patch-Clamp Techniques
gamma-Aminobutyric Acid / metabolism*
Grant Support
R01 MH066338/MH/NIMH NIH HHS; R01 MH066338-07/MH/NIMH NIH HHS
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; 0/Ion Channels; 147336-22-9/Green Fluorescent Proteins; 56-12-2/gamma-Aminobutyric Acid; EC Decarboxylase; EC decarboxylase 1; G6D6147J22/biocytin; K3Z4F929H6/Lysine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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