? Epilepsy affects 1-2% of the world's population. Given the role of voltage-gated ion channels in the regulation of neuronal excitability, there is general agreement that ion channels are involved in the pathogenesis of at least some forms of this disease. In fact, various types of epilepsy are due to mutation of genes that encode for components of voltage-gated channels selective for potassium (K+). Mice defective in the voltage-gated K+ channels Kv3.1 and Kv3.2 are epileptic, likely due to impaired cortical inhibition. This project seeks to study the role of Kv3.1/Kv3.2 in the properties of fast-spiking GABAergic interneurons (FS cells) - where these channels are specifically expressed - using dual whole-cell patch clamp recordings in the neocortex of mouse. Of particular interest are the roles of Kv3.1 and Kv3.2 in (1) neurotransmission at the FS cell terminal, and (2) the network behavior of interconnected FS cells. This project will explore the dynamics of GABA release at the FS cell terminal and its derangement in Kv3.1/3.2 knockout mice, and the disruption of synchronous FS cell behavior in these mice. This work may have implications for normal cognitive functions as well as neuropathology involving the GABAergic system, including epilepsy. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30NS047882-03
Application #
7174626
Study Section
Special Emphasis Panel (ZNS1-SRB-M (06))
Program Officer
Talley, Edmund M
Project Start
2004-12-01
Project End
2007-11-30
Budget Start
2006-12-01
Budget End
2007-11-30
Support Year
3
Fiscal Year
2007
Total Cost
$33,374
Indirect Cost
Name
New York University
Department
Physiology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Goldberg, Ethan M; Jeong, Hyo-Young; Kruglikov, Ilya et al. (2011) Rapid developmental maturation of neocortical FS cell intrinsic excitability. Cereb Cortex 21:666-82
Clark, Brian D; Goldberg, Ethan M; Rudy, Bernardo (2009) Electrogenic tuning of the axon initial segment. Neuroscientist 15:651-68
Goldberg, Ethan M; Clark, Brian D; Zagha, Edward et al. (2008) K+ channels at the axon initial segment dampen near-threshold excitability of neocortical fast-spiking GABAergic interneurons. Neuron 58:387-400
Goldberg, Ethan M; Watanabe, Shigeo; Chang, Su Ying et al. (2005) Specific functions of synaptically localized potassium channels in synaptic transmission at the neocortical GABAergic fast-spiking cell synapse. J Neurosci 25:5230-5