The role of regularity and synchrony of cerebellar Purkinje cells for pathological nystagmus.

Abstract

Previous theories assumed that the beneficial effect of the potassium channel blocker 4-aminopyridine (4-AP) for patients suffering from downbeat nystagmus (DBN) or episodic ataxia type 2 (EA2) is due to an increase of excitability of cerebellar Purkinje cells (PC). Recent experimental results using therapeutic doses of 4-AP with a mouse model of EA2 challenged the theory showing that 4-AP does not change the firing rate of PC but their regularity. Based on a mathematical model of the ocular motor and cerebellar circuitry, we show that changes in regularity have no effect without synchrony in PC firing. Together with synchronous firing, an increase in regularity may lead to a decrease in overall inhibition and may invert the inhibitory to an excitatory response due to imprinting, a novel effect of synchronized neural inhibition. Both effects are unlikely to be the causative mechanism for the success of 4-AP in treating cerebellar disorders.

• Authors: Stefan Glasauer, Christian Rössert, Michael Strupp
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1233 Pg. 162-7 (Sep 2011) ISSN: 1749-6632 [Electronic] United States
• PMID: 21950989 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 New York Academy of Sciences.

Chemical References

• Potassium Channel Blockers
• 4-Aminopyridine

Topics

• 4-Aminopyridine (therapeutic use)
• Animals
• Ataxia (drug therapy, physiopathology)
• Computer Simulation
• Disease Models, Animal
• Electrophysiological Phenomena
• Feedback, Sensory (physiology)
• Humans
• Mice
• Models, Neurological
• Nystagmus, Pathologic (drug therapy, physiopathology)
• Potassium Channel Blockers (therapeutic use)
• Purkinje Cells (drug effects, physiology)