Small conductance calcium-activated potassium (SK) channels influence the excitability of neurons and regulate synaptic plasticity, physiological processes that are fundamental for higher cognitive functions such as learning and memory. Brain circuitry that includes the hippocampus is essential for forming explicit memories, such as memory for facts, personal history and events. This project tests the influence of SK channels on brain and behavioral mechanisms of explicit memory. The central hypothesis is that SK2 channels restrict the functional output of hippocampal neurons that may be necessary for synaptic plasticity and memory. The specific aims of the studies to test this hypothesis are to: Determine the individual contributions of SK1, SK2, and SK3 channels to hippocampal learning and memory using transgenic mice strains (Aim 1). Mice that selectively lack SK2 channels are expected to have improved memory, while mice that overexpress SK2 channels are expected to have impaired memory. Determine the specific influence of hippocampal SK channels on the memory processes of encoding, retention and retrieval (Aim 2). This will be determined by direct administration of SK channel blockers or activators into the hippocampus of C57BL/6J mice. Blocking SK channels is expected to improve memory encoding, while activation of SK channels is expected to impair memory encoding. Defining how SK channels regulate hippocampal memory will improve the understanding of the behavioral and brain mechanisms of learning and memory. This project will provide opportunities for postdoctoral, graduate and undergraduate students to gain expertise in the science of learning and memory. The research will also serve as a focus for scientific outreach programs directed to the broader community.
