Asymmetric Recovery in Cerebellar-Deficient Mice Following Unilateral Labyrinthectomy

Abstract

Beraneck M, McKee JL, Aleisa M, Cullen KE. Asymmetric recovery in cerebellar-deficient mice following unilateral labyrinthectomy. J Neurophysiol 100: 945-958, 2008. First published May 28, 2008 doi:10.1152/jn.90319.2008. The term "vestibular compensation" refers to the resolution of motor deficits resulting from a peripheral vestibular lesion. We investigated the role of the cerebellum in the compensation process by characterizing the vestibuloocular reflex (VOR) evoked by head rotations at frequencies and velocities similar to those in natural behaviors in wild-type (WT) versus cerebellardeficient Lurcher (Lc/ϩ) mice. We found that during exploratory activity, normal mice produce head rotations largely consisting of frequencies Յ4 Hz and velocities and accelerations as large as 400°/s and 5,000°/s 2 , respectively. Accordingly, the VOR was characterized using sinusoidal rotations (0.2-4 Hz) as well as transient impulses (ϳ400°/s; ϳ2,000°/s 2 ). Before lesions, WT and Lc/ϩ mice produced similar VOR responses to sinusoidal rotation. Lc/ϩ mice, however, had significantly reduced gains for transient stimuli. After unilateral labyrinthectomy, VOR recovery followed a similar course for WT and Lc/ϩ groups during the first week: gain was reduced by 80% for ipsilesionally directed head rotations on day 1 and improved for both strains to values of ϳ0.4 by day 5. Moreover, responses evoked by contralesionally directed rotations returned to prelesion in both strains within this period. However, unlike WT, which showed improving responses to ipsilesionally directed rotations, recovery plateaued after first week for Lc/ϩ mice. Our results show that despite nearly normal recovery in the acute phase, long-term compensation is compromised in Lc/ϩ. We conclude that cerebellar pathways are critical for longterm restoration of VOR during head rotation toward the lesioned side, while noncerebellar pathways are sufficient to restore proper gaze stabilization during contralesionally directed movements.

Tmprss3, a Transmembrane Serine Protease Deficient in Human DFNB8/10 Deafness, Is Critical for Cochlear Hair Cell Survival at the Onset of Hearing

“…Regarding the vestibule, selective lack of saccular hair cells in Tmprss3 Y260X homozygous mice causes only a mild behavioral deficit, suggesting that other normal sensory epithelia (cristae and utricule) and probably also the vision and the CNS, as suggested in another mouse mutant, were able to partially compensate for saccular dysfunction (21). A normal number of saccular hair cells was counted in P0 Tmprss3 Y260X homozygous mice, when mechanotransduction channels are opened in vestibular hair cells (22), and no signs of hair cells loss were evident during the first postnatal days at the setup of endolymphatic composition and onset of vestibular reflexes.…”

Heat shock protein 25 expression and preferential Purkinje cell survival in the lurcher mutant mouse cerebellum

“…These findings may have broader implications for behavioral studies on the vestibulocerebellum that presume a complete lack of Purkinje cells (e.g., Koekkoek et al, 1997;LeMarec and LaLonde, 2000;Hilber and Caston, 2001;Van Alphen et al, 2002;Beraneck et al, 2008) although it is not clear whether the surviving Purkinje cells are functional.…”

Modulated discharge of Purkinje and stellate cells persists after unilateral loss of vestibular primary afferent mossy fibers in mice

“…The recovery of these reflexes is termed "vestibular compensation," and its onset can be detected both behaviorally and electrophysiologically within 10 h post-UL (Beraneck et al 2008;Precht et al 1966;Ris and Godaux 1998;Schaefer and Meyer 1973).…”

“…Recovery from major neuronal imbalance caused by a UL may obscure either the persistence or recovery from subtle cerebellar deficits tied more directly to vestibular or cerebellar dysfunction (Beraneck et al 2008). Compensation in rodents occurs within hours and is completed within 2 days.…”