Proposal #: IBN-9816865 PI Name: Paula Bickford
The proposal seeks to address the role of Norepinephrine (NE) in motor learning and plasticity in the brain. Although it has been established that NE can modulate motor learning processes, a question that remains unanswered is the site of NE's effect on motor learning. The cerebellum has been implicated because selective cerebellar depletions of NE have similar effects to what is observed with whole brain depletions of NE. The preliminary data included in this application demonstrates that propranolol, a beta-adrenergic blocker, infused into the paramedian lobe of the cerebellum impairs learning. The proposed work will narrow the site of NE's effect by continuing to perform local infusions of propranolol into the cerebellar cortex and interpositus nucleus and studying rod-running motor learning behavior.
The proposed work also addresses the control of the molecular events associated with the long-term synaptic changes produced by NE in motor learning. The PI will investigate the mechanism of induction of tissue plasminogen activator (tPA). The role of NE in tPA activation will be studied by examining tPA expression using in situ hybridization techniques in cerebellar samples from subjects that have performed the rod-running motor learning task with and without propranolol treatment.
Taken together, the work proposed would determine the molecular mechanisms that are important in the ability of NE to influence motor learning and synaptic plasticity. This information will be of significance to a wide range of neurobiologists studying numerous systems. In addition, it will be useful for understanding aging and age-related declines in motor learning.
