Understanding the neural mechanisms of learning and memory is of tremendous importance to human health. Alzheimer's Disease alone is estimated to affect 2.6-5.1 million Americans aged 65 years and older and to have annual costs exceeding $100 billion (NIH Fact Sheet: Alzheimer's Disease). Despite steady progress in understanding the neural basis of learning and memory, there are still major gaps in our understanding. These gaps make designing specific and effective treatments for memory disorders extremely challenging, if not impossible. This grant application addresses a major research gap in the neurobiology of mammalian learning and memory literature. Specifically, the bulk of the research on the neuronal substrates of mammalian learning and memory has focused on synaptic plasticity and regulation of ligand-gated ion channels. The proposed research will fill a major research gap by examining how regulation of voltage-gated ion channels contributes to mammalian learning and memory. In this research, we will utilize a form of mammalian learning and memory whose neural substrates in the cerebellum are well-understood (eyeblink conditioning) and study a voltage-gated ion channel whose regulation is well-understood and whose distribution in the cerebellum is highly localized (Kv1.2). Combining eyeblink conditioning and Kv1.2 gives us a """"""""model system"""""""" for answering general questions about how regulation of voltage-gated ion channels contributes to mammalian learning and memory. We combine behavior, intracranial infusions, and in vivo recording to explore how and when Kv1.2 function in different regions of cerebellar cortex contributes to acquisition, expression, and extinction of eyeblink conditioning in rats and we combine behavior and biochemical assays to explore how eyeblink conditioning in rats affects cerebellar cortical Kv1.2 regulation and function.
Understanding the neural mechanisms of learning and memory is of tremendous importance to human health. Despite steady progress in understanding the neural basis of learning and memory, there are still major gaps in our understanding. The proposed research will fill a major research gap by examining how regulation of voltage-gated ion channels contributes to mammalian learning and memory.
| Chihabi, Kutibh; Morielli, Anthony D; Green, John T (2016) Intracerebellar infusion of the protein kinase M zeta (PKM?) inhibitor zeta-inhibitory peptide (ZIP) disrupts eyeblink classical conditioning. Behav Neurosci 130:563-571 |
| Fuchs, Jason R; Robinson, Gain M; Dean, Aaron M et al. (2014) Cerebellar secretin modulates eyeblink classical conditioning. Learn Mem 21:668-75 |
