HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 95/3/1588    most recent 00318.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Stahl, J. S. Articles by De Zeeuw, C. I. Search for Related Content PubMed PubMed Citation Articles by Stahl, J. S. Articles by De Zeeuw, C. I.

Eye Movements of the Murine P/Q Calcium Channel Mutant Tottering, and the Impact of Aging

¹Department of Neurology, Case Western Reserve University, Cleveland; ²Department of Neurology, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio; and ³Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands

Submitted 28 March 2005; accepted in final form 2 December 2005

Mice carrying mutations of the gene encoding the ion pore of the P/Q calcium channel (Cacna1a) are an instance in which cerebellar dysfunction may be attributable to altered electrophysiology and thus provide an opportunity to study how neuronal intrinsic properties dictate signal processing in the ocular motor system. P/Q channel mutations can engender multiple effects at the single neuron, circuit, and behavioral levels; correlating physiological and behavioral abnormalities in multiple allelic strains will ultimately facilitate determining which alterations of physiology are responsible for specific behavioral aberrations. We used videooculography to quantify ocular motor behavior in tottering mutants aged 3 mo to 2 yr and compared their performance to data previously obtained in the allelic mutant rocker and C57BL/6 controls. Tottering mutants shared numerous abnormalities with rocker, including upward deviation of the eyes at rest, increased vestibuloocular reflex (VOR) phase lead at low stimulus frequencies, reduced VOR gain at high stimulus frequencies, reduced gain of the horizontal and vertical optokinetic reflex, reduced time constants of the neural integrator, and reduced plasticity of the VOR as assessed in a cross-axis training paradigm. Unlike rocker, young tottering mutants exhibited normal peak velocities of nystagmus fast phases, arguing against a role for neuromuscular transmission defects in the attenuation of compensatory eye movements. Tottering also differed by exhibiting directional asymmetries of the gains of optokinetic reflexes. The data suggest at least four pathophysiological mechanisms (two congenital and two acquired) are required to explain the ocular motor deficits in the two Cacna1a mutant strains.

This article has been cited by other articles:

				A. Katoh, J. A. Jindal, and J. L. Raymond Motor Deficits in Homozygous and Heterozygous P/Q-Type Calcium Channel Mutants J Neurophysiol, February 1, 2007; 97(2): 1280 - 1287. [Abstract] [Full Text] [PDF]