Transcript HCOP June 2010

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
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.
Parallel Fiber Stimulus  IP3
Production 
Ca2+ mobilization from ER!
Cerebellar
Purkinje
Neuron
Coincidence Detection
Supralinear Ca2+
Climbing Fiber Stimulus 
Depolarization throughout PC 
Extracellular Ca2+ entry into cell!
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
ataxic
Not
ataxic
Pathophysiology of IP3R1-associated Ataxia
Sherry-Ann Brown
Cell Biology, R.D. Berlin Center for Cell Analysis & Modeling
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
Acknowledgements
Primary Investigator:
Dr. Leslie M. Loew
Dr. Ann Cowan
Dr. Ion Moraru
Dr. James Schaff
CCAM, MD/PhD Program, UCHC
NIH
Thesis Committee
Dr. Art Hand
Dr. Bill Lytton
Dr. Marja Hurley
Dr. Raquell Holmes