The cerebellum is involved in several types of learning including fear conditioning, an animal model of post- traumatic stress disorder (PTSD). Additionally, cerebellar dysfunction is common in a number of mental illnesses, such as depression and anxiety disorders. The pathophysiology of neurological diseases involves disturbances in excitability, rhythmicity, and signaling. Animal models have implicated a role for hyperpolarization-activated cyclic nucleotide-regulated (HCN) channels in both learning and disease development. These channels are crucial in determining a neuron's intrinsic membrane properties which can ultimately affect neuronal activity and output. This proposal will investigate how learning-induced changes in hyperpolarization-activated current (Ih) of cerebellar interneurons can impact network function and behavior. Our preliminary studies show that following fear learning, there is a downregulation of HCN channels which results in reduced Ih amplitude and an increase in input resistance. The two aims in this proposal will yield different, yet complimentary findings with regards to their objective of understanding 1) changes in intrinsic membrane properties due to alterations in Ih following an associative learning paradigm and 2) the functional consequences of these changes on network activity in the cerebellar cortex. Taken together, the anticipated results of this proposal will contribute to our understanding of how fear memories are encoded. Additionally, such studies may validate HCN channels as potential therapeutic targets for neurological disorders that are associated with changes in Ih, such as epilepsy and depression.
NIH ExPorter
NIH ExPorter