Type B GABA receptors contribute to the restoration of balance during vestibular compensation in mice.
Following unilateral vestibular damage (UVD), vestibular compensation restores both static and dynamic vestibular reflexes. The cerebellar cortex provides powerful GABAergic inhibitory input to the vestibular nuclei which is necessary for compensation. Metabotropic GABA type B (GABA(B)) receptors in the vestibular nuclei are thought to be involved. However, the contribution of GABA(B) receptors may differ between static and dynamic compensation. We tested static and dynamic postural reflexes and gait in young mice, while they compensated for UVD caused by injection of air into the vestibular labyrinth. The effects of an agonist (baclofen), an antagonist (CGP56433A) and a positive allosteric modulator (CGP7930) of the GABA(B) receptor were evaluated during compensation. Static postural reflexes recovered very rapidly in our model, and baclofen slightly accelerated recovery. However, CGP56433A significantly impaired static compensation. Dynamic reflexes were evaluated by balance-beam performance and by gait; both showed significant decrements following UVD and performance improved over the next 2 days. Both CGP56433A and baclofen temporarily impaired the ability to walk on a balance beam after UVD. Two days later, there were no longer any significant effects of drug treatments on balance-beam performance. Baclofen slightly accelerated the recovery of stride length on a flat surface, but CGP7930 worsened the gait impairment following UVD. Using immunohistochemistry, we confirmed that GABA(B) receptors are abundantly expressed on the vestibulospinal neurons of Deiters in mice. Our results suggest that GABA(B) receptors contribute to the compensation of static vestibular reflexes following unilateral peripheral damage. We also conclude that impairment of the first stage of compensation, static recovery, does not necessarily result in an impairment of dynamic recovery in the long term.
Heskin-Sweezie
R
R
Department of Physiology, University of Toronto, Toronto, ON, Canada.
Titley
H K
HK
Baizer
J S
JS
Broussard
D M
DM
D000222:Adaptation, Physiological; D000818:Animals; D001259:Ataxia / Q000503:physiopathology*; D001418:Baclofen / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D007794:Lameness, Animal / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010636:Phenols / Q000494:pharmacology; D010721:Phosphinic Acids / Q000494:pharmacology; D004856:Postural Balance / Q000502:physiology*; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D020127:Recovery of Function; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D003689:Vestibular Nucleus, Lateral / Q000187:drug effects / Q000502:physiology*; D014722:Vestibule, Labyrinth / Q000293:injuries*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
C438607:2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol; D001565:Benzoates; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; C485504:Gabbr2 protein, mouse; D010636:Phenols; D010721:Phosphinic Acids; D018080:Receptors, GABA-B; C105509:(3-(1-((3-(cyclohexylmethyl)hydroxyphosphinyl)-2-hydroxypropyl)amino)ethyl)benzoic acid; D005680:gamma-Aminobutyric Acid; D001418:Baclofen
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