Vestibular compensation after unilateral labyrinthectomy: normal versus cerebellar dysfunctional mice.
BACKGROUND
Loss of vestibular information from one labyrinth produces marked asymmetries of postural and ocular motor control, which resolve over time. Recent developments in mouse genetic engineering, which allow the generation of transgenic and knockout mutant mice, provide a unique opportunity to bridge the gap between the molecular mechanisms that underlie compensation and behaviour.


METHODS
We compared compensation following unilateral labyrinthectomy in wild-type mice and a cerebellar-dysfunctional mouse (the Lurcher mutant). The Lurcher mutant is characterized by a point mutation in the ionotropic glutamate receptor delta 2 subunit gene that results in loss of all Purkinje cells. To further investigate this question, we characterized vestibular compensation in a strain of mutant mice that completely lack cerebellar Purkinje cells.


RESULTS
Static signs resolved within 24 hours in wild-type mice but did not fully resolve in Lurcher mice. Dynamic signs were evaluated by the quantitative analysis of vestibulo-ocular (VOR) and vestibulocollic (VCR) reflexes. The VOR assessed at 0.5 Hz exhibited increasing gain from day 1 to day 5, reaching control levels by day 20 for the wild-type mice. In contrast, Lurcher mutant mice showed significantly less compensation over this same period. VOR compensation in the mutant mice was slightly more robust in response to high acceleration thrusts but again never reached control levels. Similarly, VCR gains showed limited compensation and remained subnormal in mutant mice.


CONCLUSIONS
Compensation for dynamic signs starts at day 5 after unilateral labyrinthectomy in normal mice. Cerebellar dysfunctional mutant mice do not compensate for static signs and show limited vestibular compensation for dynamic signs only. We conclude that other noncerebellar pathways for vestibular compensation exist, and our findings emphasize the need for these to be further explored.
Aleisa
Mohammad
M
Department of Otolaryngology, McGill University Health Centre, Montreal, QC, Canada.
Zeitouni
Anthony G
AG
Cullen
Kathleen E
KE
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D002531:Cerebellum / Q000502:physiology; D005133:Eye Movements / Q000502:physiology; D019416:Head Movements / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants; D009760:Nystagmus, Physiologic / Q000502:physiology; D013506:Otologic Surgical Procedures; D011689:Purkinje Cells / Q000502:physiology; D012027:Reflex, Vestibulo-Ocular / Q000502:physiology*; D014722:Vestibule, Labyrinth / Q000601:surgery*