Early and late changes in vestibular neuronal excitability after deafferentation

Abstract

Medial vestibular nucleus neurons develop a sustained increase in electrophysiological excitability after deafferentation, which may be an important component of 'vestibular compensation' (the behavioural recovery that follows peripheral vestibular lesions). We investigated the effects of gamma-aminobutyric acid, glutamate and glycine receptor blockade on the spontaneous activity of deafferented medial vestibular nucleus neurons in slices, to determine whether changes in synaptic inputs contribute to their increased excitability. Soon after deafferentation (4 h after labyrinthectomy) synaptic blockade had no effect on the elevated in-vitro firing of medial vestibular nucleus neurons, while later (48 h, 1 week), synaptic blockade reduced the elevated activity to normal. Intrinsic mechanisms therefore appear to mediate the elevated excitability of medial vestibular nucleus cells initially after deafferentation. Subsequently, changes in the efficacy of synaptic inputs are implicated, presumably involving intranuclear projections that are preserved in slices.

Sequential [18F]FDG µPET whole-brain imaging of central vestibular compensation: a model of deafferentation-induced brain plasticity

“…Corresponding transversal slices of a brain atlas are shown on the right side. L left side, R right side Vestibular nuclei re-balancing It has been reported that during the initial phase of vestibular compensation (4-24 h post unilateral labyrinthectomy) a restoration of spontaneous activity of ipsilesional secondorder vestibular neurons and bilateral re-balancing of resting firing rates occurs which is due to changes in membrane properties (Precht et al 1966;Smith and Curthoys 1988;Cameron and Dutia 1997;Guilding and Dutia 2005;Bergquist et al 2008;Lim et al 2010;Shao et al 2012). This intrinsic hyperactivity may be related to firing rate potentiation or rapid down-regulation of GABA receptors (Yamanaka et al 2000;Nelson et al 2003;Bergquist et al 2008).…”

“…Corresponding transversal slices of a brain atlas are shown on the right side. L left side, R right side Table 1 shows all significant rCGM changes following surgical unilateral labyrinthectomy for all relevant anatomic regions as a function of time Decrease of rCGM is depicted in Italic, increase in Bold L left side, R right side The significance of the clusters is depicted by t-values at a p value of 0.001 or 0.01 (the latter indicated by *) Surgical unilateral labyrinthectomy 4 h 1 day 2 day 3 day 7 day 9 day from 2 days on are followed by changes of spontaneous activity that depend on synaptic inputs (Guilding and Dutia 2005). The vestibular nuclei are embedded in sensorimotor networks, through which proprioceptive information reaches the vestibular nuclei from the central cervical and spinal trigeminal nucleus (Sato et al 1997).…”

Reconsidering the Role of Neuronal Intrinsic Properties and Neuromodulation in Vestibular Homeostasis

“…This synaptic uncoupling can be achieved by modifying the artificial cerebro-spinal fluid (ACSF), e.g., with high Mg 2+ /low Ca 2+ ACSF (Vibert et al, 2000; Darlington et al, 2002), or with a cocktail of synaptic blockers (Ris et al, 2001a; Guilding and Dutia, 2005) as well as by complete isolation from other structures (Darlington and Smith, 2000). The 2° VN intrinsic properties, and in particular those of neurons from the medial vestibular nucleus, have been described in many Vertebrates, including Rats (Gallagher et al, 1985; Johnston et al, 1994), Mice (Dutia et al, 1995; Johnston and Dutia, 1996), Guinea pigs (Serafin et al, 1991a,b), Amphibians (Straka et al, 2004), and Chicks (du Lac and Lisberger, 1995; Gottesman-Davis and Peusner, 2010; Gottesman-Davis et al, 2011).…”

“…This increase in spontaneous activity is however transitory and concerns the rostral, but not the caudal, part of the medial vestibular nuclei. Indeed, from the second day onward, increase in the spontaneous activity critically depends on synaptic inputs as demonstrated using cocktails of antagonists (Guilding and Dutia, 2005). Interestingly, intracellular recordings suggest that the ipsilesional type B neurons are preferentially affected, while type A neurons appear left untouched until the 7–11th day after the lesion (Him and Dutia, 2001).…”

Neurobiological Mechanisms of Acute Vertigo

“…Potential underlying mechanisms allowing such changes in MVN neuronal excitability are intracellular modulations of electrolyte levels including calcium and potassium [42], the down-regulation of inhibitory GABA [34] and glycine receptors [43] and the increased activation of glucocorticoid receptors [39]. Guilding and Dutia [44] applied a synaptic blockade of GABA, glycine and glutamate receptors in vitro to evaluate its impact on intrinsic excitability of deafferented MVN neurons in rats. They proposed that the increase in intrinsic excitability after UVD follows two stages: 1) in the very early stage, increases in excitability seem to be mediated by intrinsic cellular mechanisms (e.g.…”