A fundamental feature of cortical neurons is the way they transform input current into action potential output. Many cortical neurons adapt: the interval between successive action potentials increases in response to constant current injection. The ion channels mediating this behavior have been sought for more than two decades. We discovered that corticospinal neurons in motor cortex have the opposite behavior: the interval between successive action potentials decreases. The mechanisms of this firing rate acceleration are also not known. We have used microarrays to profile gene expression in distinct populations of cortical neurons. These experiments have identified potassium channels that may underlie adaptation and acceleration. Here we will test the role of these channels in endowing cortical cell types with distinct firing properties. We will determine how firing properties differ across anatomically and genetically defined cell types and how these properties vary across cortical regions. We will also study the emergence of cell type specific firing properties during development, and determine whether or not the development and maintenance of intrinsic firing properties is activity dependent. Significance: Cortical circuits malfunction in epilepsy, stroke and developmental disorders such as mental retardation and autism. Understanding the molecular and physiological properties that distinguish different classes of neurons that make up cortical circuits may illuminate the malfunction of these circuits during disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH066338-10
Application #
8109921
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Asanuma, Chiiko
Project Start
2002-08-01
Project End
2012-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
10
Fiscal Year
2011
Total Cost
$350,395
Indirect Cost
Name
Brandeis University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
Miller, Mark N; Okaty, Benjamin W; Kato, Saori et al. (2011) Activity-dependent changes in the firing properties of neocortical fast-spiking interneurons in the absence of large changes in gene expression. Dev Neurobiol 71:62-70
Okaty, Benjamin W; Sugino, Ken; Nelson, Sacha B (2011) Cell type-specific transcriptomics in the brain. J Neurosci 31:6939-43
Nagoshi, Emi; Sugino, Ken; Kula, Ela et al. (2010) Dissecting differential gene expression within the circadian neuronal circuit of Drosophila. Nat Neurosci 13:60-8
Kadener, Sebastian; Menet, Jerome S; Sugino, Ken et al. (2009) A role for microRNAs in the Drosophila circadian clock. Genes Dev 23:2179-91
Okaty, Benjamin W; Miller, Mark N; Sugino, Ken et al. (2009) Transcriptional and electrophysiological maturation of neocortical fast-spiking GABAergic interneurons. J Neurosci 29:7040-52
Kadener, Sebastian; Rodriguez, Joseph; Abruzzi, Katharine Compton et al. (2009) Genome-wide identification of targets of the drosha-pasha/DGCR8 complex. RNA 15:537-45
Nelson, Sacha B; Turrigiano, Gina G (2008) Strength through diversity. Neuron 60:477-82
Chen, Bin; Wang, Song S; Hattox, Alexis M et al. (2008) The Fezf2-Ctip2 genetic pathway regulates the fate choice of subcortical projection neurons in the developing cerebral cortex. Proc Natl Acad Sci U S A 105:11382-7
Miller, Mark N; Okaty, Benjamin W; Nelson, Sacha B (2008) Region-specific spike-frequency acceleration in layer 5 pyramidal neurons mediated by Kv1 subunits. J Neurosci 28:13716-26
Hattox, Alexis M; Nelson, Sacha B (2007) Layer V neurons in mouse cortex projecting to different targets have distinct physiological properties. J Neurophysiol 98:3330-40

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