title: Behavioral motor dysfunction in Kv3-type potassium channel-deficient mice.
abstract: The voltage-gated potassium channels Kv3.1 and Kv3.3 are expressed in several distinct neuronal subpopulations in brain areas known to be involved in motor control such as cortex, basal ganglia and cerebellum. Depending on the lack of Kv3.1 or Kv3.3 channel subunits, mutant mice show different Kv3-null allele-dependent behavioral alterations that include constitutive hyperactivity, sleep loss, impaired motor performance and, in the case of the Kv3.1/Kv3.3 double mutant, also severe ataxia, tremor and myoclonus (Espinosa et al. 2001, J Neurosci 21, 6657-6665, Genes, Brain Behav 3, 90-100). The lack of Kv3.1 channel subunits is mainly responsible for the constitutively increased locomotor activity and for sleep loss, whereas the absence of Kv3.3 subunits affects cerebellar function, in particular Purkinje cell discharges and olivocerebellar system properties (McMahon et al. 2004, Eur J Neurosci 19, 3317-3327). Here, we describe two sensitive and non-invasive tests to reliably quantify normal and abnormal motor functions, and we apply these tests to characterize motor dysfunction in Kv3-mutant mice. In contrast to wildtype and Kv3.1-single mutants, Kv3.3-single mutants and Kv3 mutants lacking three and four Kv3 alleles display Kv3-null allele-dependent gait alterations. Although the Kv3-null allele-dependent gait changes correlate with reduced motor performance, they appear to not affect the training-induced improvement of motor performance. These findings suggest that altered cerebellar physiology in the absence of Kv3.3 channels is responsible for impaired motor task execution but not motor task learning.
authors.affiliation: Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA. rolf.joho@utsouthwestern.edu
authors.forename: R H
authors.initials: RH
authors.lastname: Joho
authors.forename: C
authors.initials: C
authors.lastname: Street
authors.forename: S
authors.initials: S
authors.lastname: Matsushita
authors.forename: T
authors.initials: T
authors.lastname: Knöpfel
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002531:Cerebellum / Q000378:metabolism* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D020233:Gait Disorders, Neurologic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D007858:Learning / Q000502:physiology; D007859:Learning Disabilities / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009068:Movement / Q000502:physiology; D009069:Movement Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D009483:Neuropsychological Tests; D051670:Shaw Potassium Channels / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D051670:Shaw Potassium Channels