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Loss of sensory input from one vestibular labyrinth by unilateral vestibular deafferentation (UVD) results in a severe ocular motor (i.e., spontaneous nystagmus (SN)) and postural syndrome (i.e., yaw head tilt, (YHT) and roll head tilt (RHT)) which compensates over time in a behavioural recovery process known as vestibular compensation. It is generally accepted that the UVD-induced neuronal imbalance in the resting activity between the two vestibular nuclear complexes (VNCs) generates the ocular motor and postural syndrome and that the restoration of the resting activity in the ipsilateral VNC plays a causal role in the compensation of the static symptoms. γ-Aminobutyric acid (GABA) and the GABAA and GABAB receptors within the VNC are involved in normal vestibulo-ocular and --spinal pathways and it has been suggested that modification of GABAergic inhibition may be a mechanism responsible for the recovery of resting activity in the ipsilateral VNC. Behavioural, western blotting, and immunoassay techniques were used to address the role of the GABAA receptor in the VNC during vestibular compensation. The first study involved the characterization of SN, YHT, and RHT compensation in guinea pigs that had been anaesthetized with isoflurane during the UVD. These animals compensated rapidly (i.e., 30 hrs) and the time to compensate was independent of the duration of the anaesthesia. Using the 30 hrs time frame, the effects of the chronic infusion of the GABAA receptor agonist (muscimol) / antagonist (gabazine) into either the ipsilateral or the contralateral VNC on the compensation of SN, YHT, and RHT, were determined. Infusion of muscimol (250, 500, and 750 ng) into the contralateral VNC and gabazine (31.25, 62.5 and 125 ng) into the ipsilateral VNC significantly affected YHT and RHT (p < 0.05), but not their rate of compensation (p > 0.05). Interestingly, the effects of muscimol and gabazine on YHT and RHT were consistent throughout the first 30 hrs post-UVD. At 30 hrs post-UVD, the pumps were disconnected. In both experimental groups, the value and direction of the YHT and RHT returned to vehicle levels. Infusion of muscimol (62.5, 125, and 250 ng) into the ipsilateral VNC and gabazine (125, 375, and 750 ng) into the contralateral VNC had little effect on YHT and RHT, or their rate of compensation. At 30 hrs post-UVD, the pumps were disconnected. In both experimental groups, the value and direction of the YHT and RHT returned to vehicle levels. These results suggest that the ipsilateral gabazine and contralateral muscimol infusions were modifying the expression of the symptoms without altering the mechanism of compensation. Furthermore, the mechanism responsible for vestibular compensation can cope with the both the GABAA receptor-mediated and the UVD-induced decrease in resting activity. Results from the western blotting study indicated that compensation of SN, YHT, and RHT is not associated with changes in the protein levels of the GABAA receptor α₁, β₂, or γ₂ subunits. Compensation of SN, YHT, and RHT is associated with an elevation in cortisol salivary levels. Overall, the results suggest that the GABAA receptors are involved in the expression of YHT and RHT, but not in the mechanism that is responsible for their compensation. |
