The long-term goal of this research program is to provide an understanding of the role(s) of voltage-gated K+ channels in the functioning of identified cortical neurons and specific cortical circuits. Multiple types of voltage-gated K+ currents have been distinguished electro physiologically in cortical neurons and a number of K+ channel Kv pore forming (alpha) and accessory (beta, KChlPs, MiRPs) subunits thought to underlie these channels have been identified. The relationships between these subunits and the K+ channels expressed in cortical neurons, however, are poorly understood. In addition, the roles of the various voltage-gated K+ currents expressed in cortical neurons in shaping action potential waveforms and in mediating repetitive firing properties remain to be defined. In the experiments proposed here, we exploit molecular genetic strategies in vivo and in vitro to identify directly the molecular correlates of the voltage-gated K+ channel currents, IA, ID and IK, expressed in superior colliculus-projecting (SCP) neurons in (mouse) primary visual cortex. In addition, we propose to define the functional roles of IA, ID and IK in shaping the waveforms of individual action potentials and in mediating repetitive firing in SCP neurons. The first three aims will define the roles of Kv4.
x (aim #1), Kv1.
x (aim #2) and Kv2.
x (aim #3) alpha subunits in the generation of IA, ID and IK, respectively, in SCP neurons, and explore the role(s) of these currents in shaping the waveforms of action potentials and in mediating repetitive firing in SCP neurons.
In aim #4, the functional role(s) of Kv beta1 subunits in the generation of the voltage-gated K+ currents expressed in SCP neurons will be explored. A sophisticated combination of biochemical, immunohistochemical, molecular, and electrophysiological techniques will be exploited to achieve these aims. The studies proposed here will provide important new insights into the molecular correlates, the distributions, and the functional roles of the voltage-gated K+ channels expressed in cortical projection neurons. In addition, these studies will provide the foundation for future efforts aimed at determining the role(s) of voltage-gated K+ channels in controlling cellular responses to synaptic inputs and the plasticity of cortical circuits, as well as the molecular mechanisms involved in mediating these effects.
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