Differential regulation of GABAA and GABAB receptors during vestibular compensation

Abstract

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.

Functional Organization of Vestibular Commissural Connections in Frog

“…9E 3 ). This GABA receptor subtype is implicated in the postlesional plasticity of the vestibular commissural circuitry after unilateral labyrinthectomy (Johnston et al, 2001;Bergquist et al, 2008). Application of CGP 35348 reduced the amplitude of the canal commissural IPSPs with a disynaptic onset (Fig.…”

Asymmetric Recovery in Cerebellar-Deficient Mice Following Unilateral Labyrinthectomy

“…6). Prior work has shown substantial changes in the intrinsic membrane properties of central vestibular neurons (Beraneck et al 2003;2004;Cameron andDutia 1997, 1999;Darlington et al 2002;Him and Dutia 2001;Ris et al 2002;see Straka et al 2005 for a review), and synaptic reorganization of the brain stem vestibular pathways (Goto et al 2000(Goto et al -2002Johnston et al 2001;Vibert et al 2000;Yamanaka et al 2000;see Dieringer 2003) following UL. Notably, Johnston and colleagues (2002) have suggested that while the increase in intrinsic excitability that develops in ipsilesional MVN neurons during vestibular compensation is cerebellar dependent and depends on glucocorticoid activation, the simultaneous downregulation of functional efficacy of GABA receptors that also occurs after UL is not.…”

Morphofunctional Correlation of Excitatory and Depressor Synaptic Processes in Hippocampus, Amygdala and Basal Meynert Nucleus Neurons in Dynamics of Development of Alzheimer's Disease Model Induced by Aβ25-35

“…According to recent data, it suggested that GABA and glycine can play an important in the developing and mature central vestibular system [67]. In turn, in neurons of the vestibular nuclei by the GABA receptor mediated vestibular compensation after unilateral labyrinthectomy [67][68][69][70]. In this paper, where besides H for the first time are studied of Am and NM on the model of AD and also it is possible the involvement of true GABAergic inhibition during tetanic depression, with the aim of its deepening in the structures studied, thus supposed need of protectors for therapeutic intervention in the process of de and regeneration.…”