? 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. ? ?
| 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 |
