Simulation of alcohol action upon a detailed Purkinje neuron model and a simpler surrogate model that runs >400 times faster.
BACKGROUND
An approach to investigate brain function/dysfunction is to simulate neuron circuits on a computer. A problem, however, is that detailed neuron descriptions are computationally expensive and this handicaps the pursuit of realistic network investigations, where many neurons need to be simulated.


RESULTS
We confront this issue; we employ a novel reduction algorithm to produce a 2 compartment model of the cerebellar Purkinje neuron from a previously published, 1089 compartment model. It runs more than 400 times faster and retains the electrical behavior of the full model. So, it is more suitable for inclusion in large network models, where computational power is a limiting issue. We show the utility of this reduced model by demonstrating that it can replicate the full model's response to alcohol, which can in turn reproduce experimental recordings from Purkinje neurons following alcohol application.


CONCLUSIONS
We show that alcohol may modulate Purkinje neuron firing by an inhibition of their sodium-potassium pumps. We suggest that this action, upon cerebellar Purkinje neurons, is how alcohol ingestion can corrupt motor co-ordination. In this way, we relate events on the molecular scale to the level of behavior.
Department of Computer Science, University of Warwick, Coventry, West Midlands, UK. mikeforrest@hotmail.com.
Michael D
MD
Forrest
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000465:Algorithms; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003198:Computer Simulation; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008959:Models, Neurological; D011689:Purkinje Cells / Q000187:drug effects* / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
D002492:Central Nervous System Depressants; D051036:Large-Conductance Calcium-Activated Potassium Channels; D000431:Ethanol; D000254:Sodium-Potassium-Exchanging ATPase