The long term goal of this project is to contribute to the understanding of the role of K+ channel diversity in the central nervous system (CNS). K+ channels regulate neuronal excitability. They underlie many of the differences in functional properties that characterize specific neurons, contributing to the complexity of neuronal information coding and integration. It is hypothesized that their diversity provides signaling specificity to neuronal circuits and to the actions of neurotransmitters. Mutations in genes encoding K+ channels have been found to cause epilepsy and other types of human disease. This proposal focuses on a subtype of cortical GABAergic inhibitory interrneuron known as the fast-spiking (FS) cell, named for its ability to fire sustained trains of action potentials (APs) at remarkably high frequencies. GABAergic interneurons are key components of the cerebral cortex and have essential roles in information processing, plasticity, the generation of cortical rhythms, and in the pathogenesis of seizures. Knowledge of the molecular elements responsible for FS cell function is critical for the manipulation of cortical function to understand physiological and pathophysiological conditions and to provide targets for therapeutic drugs. It has been demonstrated that K+ channels of the Kv3 subfamily contribute to the ability of FS cells to fire at high frequency and preliminary evidence shows that the same channels have a key role in the regulation of synaptic transmission from FS cell terminals. Two additional types of K+ channels have also been found at the FS cell synapse.
Aim I will utilize electrophysiological recordings in acute slices from primary somatosensory cortex in mice to investigate the functions of the three types of K+ channels so far discovered at FS terminals. Immunolocalization will be used to investigate how localization within the synapse affects the roles of each type of channel.
Aim II will utilize electrophysiological recordings from electrically and chemically connected FS cells to understand the role of these channels in generating synchronous activity within FS cell networks.
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