1. Virtual NEURON: A Unifying Computational Framework to Study Calcium Signaling and Membrane Electrophysiology in Physiological Cerebellar Purkinje Neurons & in IP3R1-associated Ataxias Sherry-Ann Brown, M2G4 Loew Lab, UCHC

2. The Cerebellum Latin, little brain Constitutes only 10% of the total volume of the brain, but contains more than half of all its neurons 40 times more axons project into the cerebellum than exit from it Controls posture and locomotion Coordinates gaze, speech, handwriting, and other motor functions The Cerebellum, Principles of Neural Science. 2000 McGraw Hill. ATAXIA n. Loss of motor coordination.

3. Climbing Fiber Stimulus  Depolarization throughout PC  Extracellular Ca2+ entry into cell! Parallel Fiber Stimulus  IP3 Production  Ca2+ mobilization from ER! Coincidence Detection Supralinear Ca2+ Cerebellar Purkinje Neuron

4. Reaction Diagram

5. SIX Spines - Simulation Max 8120 1400 Min

6. Application Accurate, physiological models can be useful in addressing pathophysiology and perhaps therapeutic intervention of ataxia. "Ataxia has taught me to never take the abilities to do various things for granted, such as walking, talking, carrying a cup of tea without spilling it, walking up or down steps, and so many things.” ~ Individual living with SCA

7. How can we restore ‘normal’ calcium response? Reduced Abundance Increased Sensitivity

8. Ataxic Mouse on a Rotating Rod Not ataxic

9. Pathophysiology of IP3R1-associated Ataxia Sherry-Ann Brown Cell Biology, R.D. Berlin Center for Cell Analysis & Modeling

10. Poetic Science - Collection © 2010 Sherry-Ann Brown Poetic Science Scientific Birth I Love the Spine Neck Coincident Incident How Will I Dance? Ataxic MatchMaker A Delicate Dance Awestillation Just One More Step

11. Acknowledgements CCAM, MD/PhD Program, UCHC NIH Thesis Committee Primary Investigator: Primary Investigator: Dr. Leslie M. Loew Dr. Ion Moraru Dr. James Schaff Dr. Ann Cowan Dr. Raquell Holmes Dr. Art Hand Dr. Bill Lytton Dr. Marja Hurley