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 #
5R01MH066338-07
Application #
7501502
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Asanuma, Chiiko
Project Start
2002-08-01
Project End
2012-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
7
Fiscal Year
2008
Total Cost
$351,897
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
Okaty, Benjamin W; Sugino, Ken; Nelson, Sacha B (2011) Cell type-specific transcriptomics in the brain. J Neurosci 31:6939-43
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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
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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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