Virtual NEURON A Unifying Computational Framework to Study

Virtual NEURON: A Unifying Computational Framework to Study Calcium Signaling and Membrane Electrophysiology in Physiological Cerebellar Purkinje Neurons & in IP 3 R 1 -associated Ataxias Sherry-Ann Brown, M 2 G 4 Loew Lab, UCHC

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 Mc. Graw Hill. ATAXIA n. Loss of motor coordination.

Parallel Fiber Stimulus IP 3 Production Ca 2+ mobilization from ER! Cerebella r Purkinje Neuron Coincidence Supralinear Ca 2+ Detection Climbing Fiber Stimulus Depolarization throughout PC Extracellular Ca 2+ entry into

Reaction Diagram

SIX Spines - Simulation Max 8120 1400 Min

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

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

Ataxic Mouse on a Rotating Rod Not ataxi c

Pathophysiology of IP 3 R 1 -associated Ataxia

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

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