GABAergic systems in the vestibular nucleus and their contribution to vestibular compensation.
GABA and the GABAA and GABAB receptors play a pivotal role in the coordination of the central vestibular pathways. The commissural inhibition, which exists between the two vestibular nucleus complexes (VNCs) and which is responsible for enhancing the dynamic sensitivity of VNC neurons to head acceleration, is known to be substantially mediated by GABA acting on GABAA and GABAB receptors. After unilateral vestibular deafferentation (UVD), the large asymmetry in spontaneous resting activity between the two VNCs is reinforced and exacerbated by the GABAergic interaction between the ipsilateral and contralateral sides. Although it has been suggested that reduced GABAergic inhibition of the ipsilateral VNC may be partially responsible for the recovery of resting activity that underlies vestibular compensation of the static symptoms of UVD, at present there are few data available to test this hypothesis systematically. There is some evidence that GABA concentrations change in the ipsilateral VNC during the development of compensation; however, it is unclear whether these changes relate to GABA release or to metabolic pools of GABA. Most biochemical studies of GABA receptors have been conducted at the gene expression level. Therefore, it is unclear whether changes in the receptor protein also occur, although the most recent data suggest that changes in GABAA and GABAB receptor density in the VNC are unlikely. The few radioligand binding data relate to GABAA receptors with benzodiazepine binding sites only. A decrease in the sensitivity of ipsilateral VNC neurons from compensated animals to GABA receptor agonists has been reported; however, these studies have employed brainstem slices and therefore the functional identity of the neurons involved has been unclear. Although it seems likely that some changes in central GABAergic systems accompany the recovery of resting activity in the ipsilateral VNC during the development of vestibular compensation, at the present stage there is no compelling evidence that these changes have a causal role in the compensation process.
Gliddon
Catherine M
CM
Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.
Darlington
Cynthia L
CL
Smith
Paul F
PF
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology*; D015837:Vestibular Diseases / Q000503:physiopathology*; D014726:Vestibular Nuclei / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid