Differential regulation of GABA(A) and GABA(B) receptors during vestibular compensation.
We investigated changes in intrinsic excitability and GABA receptor efficacy in rat medial vestibular nucleus (MVN) neurons following 48 h and 7-10 days of behavioral recovery after unilateral labyrinthectomy (UL) in the rat. The mean in vitro discharge rate of rostral ipsilesional MVN cells at both time points was significantly higher than normal, indicating that the intrinsic excitability of the deafferented cells undergoes a sustained up-regulation during vestibular compensation. In slices from animals that had compensated for 7-10 days after UL, the responsiveness of rostral ipsilesional MVN cells to the GABA(A) agonist muscimol was not different from normal, while the responsiveness to the GABA(B) agonist baclofen was significantly down-regulated. This is in contrast to the situation soon after UL, where the efficacy of both GABA(A) and GABA(B) receptors is markedly down-regulated. The recovery of fast GABA(A) mediated neurotransmission by 7-10 days post-UL presumably enables ipsilesional cells to again respond to vestibular stimulation, through commissural inhibitory modulation from the intact side. The permanent loss of excitatory input from the lesioned side may be, in effect, counteracted by the long-term down-regulation of slow GABA(B) receptors in the de-afferented neurons.
Department of Biomedical Sciences (Physiology), University of Edinburgh Medical School, UK.
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Johnston
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Dutia
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D007758:Ear, Inner / Q000502:physiology / Q000601:surgery; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D014726:Vestibular Nuclei / Q000166:cytology / Q000378:metabolism*
D018755:GABA Agonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D009118:Muscimol; D001418:Baclofen