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.

Public Health Relevance

Cerebellar dysfunction is common in a number of mental illnesses, such as depression and anxiety disorders which could involve disturbances in neuronal excitability, rhythmicity, and signaling. Animal models have implicated changes in HCN channels and Ih as critical components of disease development. Our investigation of changes in HCN channels in an animal model of PTSD could contribute to our understanding of how fear memories are encoded;such studies may validate HCN channels as potential therapeutic targets for neurological disorders that are associated with changes in Ih, such as epilepsy.

Agency
National Institute of Health (NIH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32MH103964-01
Application #
8713355
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Desmond, Nancy L
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Louisiana State Univ Hsc New Orleans
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70112