Effects of Chronic Infusion of a GABA<sub>A</sub> Receptor Agonist or Antagonist into the Vestibular Nuclear Complex on Vestibular Compensation in the Guinea Pig

Gliddon, Catherine M.; Darlington, Cynthia L.; Smith, Paul F.

doi:10.1124/jpet.104.082172

Cited by 15 publications

(6 citation statements)

References 37 publications

(52 reference statements)

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“…Since oculomotor function recovery is faster than posturo-locomotor recovery and depends on different plasticity mechanisms, we propose that this bilateral GAD67 increased expression would be a plastic neurochemical mechanism involved in the posturo-locomotor recovery and in its long-term maintenance. In line with this, chronic infusion of GABA A receptor antagonists in the deafferented VN of vestibulo-lesioned guinea pigs modified the expression of postural symptoms, with no alteration of the oculomotor deficits [36]. Moreover, antimitotic drugs that block reactive cell proliferation after UVN drastically delay only the posturo-locomor functions and have no incidence on horizontal nystagmus [10].…”

Section: Discussionmentioning

confidence: 58%

“…GABA and its two receptors GABA A and GABA B are known to coordinate the vestibular pathways and to restore vestibular functions [34]. Injections or infusions of GABA A antagonists accelerate postural recovery of vestibular deafferented animals, while GABA A agonists have opposite effects [35], [36]. Interestingly, in accordance with results of Tighilet and Lacour [37] that observed a bilateral GAD67 increased expression in the VN one year after UVN, we also observed a bilateral GAD67 increased expression in the VN as soon as two months after UVN.…”

Section: Discussionmentioning

confidence: 99%

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Neurogenic Potential of the Vestibular Nuclei and Behavioural Recovery Time Course in the Adult Cat Are Governed by the Nature of the Vestibular Damage

2011

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Functional and reactive neurogenesis and astrogenesis are observed in deafferented vestibular nuclei after unilateral vestibular nerve section in adult cats. The newborn cells survive up to one month and contribute actively to the successful recovery of posturo-locomotor functions. This study investigates whether the nature of vestibular deafferentation has an incidence on the neurogenic potential of the vestibular nuclei, and on the time course of behavioural recovery. Three animal models that mimic different vestibular pathologies were used: unilateral and permanent suppression of vestibular input by unilateral vestibular neurectomy (UVN), or by unilateral labyrinthectomy (UL, the mechanical destruction of peripheral vestibular receptors), or unilateral and reversible blockade of vestibular nerve input using tetrodotoxin (TTX). Neurogenesis and astrogenesis were revealed in the vestibular nuclei using bromodeoxyuridine (BrdU) as a newborn cell marker, while glial fibrillary acidic protein (GFAP) and glutamate decarboxylase 67 (GAD67) were used to identify astrocytes and GABAergic neurons, respectively. Spontaneous nystagmus and posturo-locomotor tests (static and dynamic balance performance) were carried out to quantify the behavioural recovery process. Results showed that the nature of vestibular loss determined the cellular plastic events occurring in the vestibular nuclei and affected the time course of behavioural recovery. Interestingly, the deafferented vestibular nuclei express neurogenic potential after acute and total vestibular loss only (UVN), while non-structural plastic processes are involved when the vestibular deafferentation is less drastic (UL, TTX). This is the first experimental evidence that the vestibular complex in the brainstem can become neurogenic under specific injury. These new data are of interest for understanding the factors favouring the expression of functional neurogenesis in adult mammals in a brain repair perspective, and are of clinical relevance in vestibular pathology.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Neurogenic Potential of the Vestibular Nuclei and Behavioural Recovery Time Course in the Adult Cat Are Governed by the Nature of the Vestibular Damage

2011

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“…Muscimol was diluted to the required concentration using artificial cerebrospinal fluid (124 mM NaCl, 5 mM KCl, 1.2 mM KH2PO4, and 1.3 mM MgSO4) and tested for pH and adjusted to a pH 7.0, if necessary. As detailed in the study of Gliddon et al (2005), we chose concentrations that provided an effect on vestibular neurogenesis without adverse side effects on animals (Dutheil et al, 2013). AraC was diluted in a NaCl solution at 0.13 mM, this concentration was demonstrated to inhibit totally the mitotic activity in the deafferented vestibular nuclei without adverse side effects on animals (Dutheil et al, 2009).…”

Section: Methodsmentioning

confidence: 99%

Reactive Neurogenesis and Down-Regulation of the Potassium-Chloride Cotransporter KCC2 in the Cochlear Nuclei after Cochlear Deafferentation

et al. 2016

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While many studies have been devoted to investigating the homeostatic plasticity triggered by cochlear hearing loss, the cellular and molecular mechanisms involved in these central changes remain elusive. In the present study, we investigated the possibility of reactive neurogenesis after unilateral cochlear nerve section in the cochlear nucleus (CN) of cats. We found a strong cell proliferation in all the CN sub-divisions ipsilateral to the lesion. Most of the newly generated cells survive up to 1 month after cochlear deafferentation in all cochlear nuclei (except the dorsal CN) and give rise to a variety of cell types, i.e., microglial cells, astrocytes, and neurons. Interestingly, many of the newborn neurons had an inhibitory (GABAergic) phenotype. This result is intriguing since sensory deafferentation is usually accompanied by enhanced excitation, consistent with a reduction in central inhibition. The membrane potential effect of GABA depends, however, on the intra-cellular chloride concentration, which is maintained at low levels in adults by the potassium chloride co-transporter KCC2. The KCC2 density on the plasma membrane of neurons was then assessed after cochlear deafferentation in the cochlear nuclei ipsilateral and contralateral to the lesion. Cochlear deafferentation is accompanied by a strong down-regulation of KCC2 ipsilateral to the lesion at 3 and 30 days post-lesion. This study suggests that reactive neurogenesis and down-regulation of KCC2 is part of the vast repertoire involved in homeostatic plasticity triggered by hearing loss. These central changes may also play a role in the generation of tinnitus and hyperacusis.

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“…En adéquation avec cette hypothèse, les travaux d'une équipe de chercheurs néo-zélandais ont montré qu'après lésion vestibulaire unilatérale, l'infusion d'oligonucléotides antisens bloquant l'expression du BDNF (facteur favorisant entre autres la neurogenèse) chez la souris conduisait à un retard dans la compensation des déficits posturaux, sans incidence sur le nystagmus oculaire [33]. Dans une autre étude, l'infusion chronique d'antagonistes des récepteurs GABA A dans les NV désafféren-tés a modifié l'expression des symptômes posturaux chez le cochon d'Inde, sans altérer l'expression des symptômes oculomoteurs [34]. Ainsi la compensation des paramètres posturolocomoteurs et oculomoteurs serait gouvernée par des mécanismes de plasticité différents.…”

Section: Neurogenèse Des Nv Et Restauration Des Fonctions Posturo-locunclassified

Une nouvelle zone de neurogenèse fonctionnelle

2011

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> En dehors de deux structures précises : la zone sous-granulaire et la zone sous-ventriculaire, le cerveau du mammifère adulte est considéré comme non neurogène, c'est-à-dire incapable de produire de nouveaux neurones. Cependant, les influences environnementales qui s'opposent à cette activité peuvent être mises entre parenthèses dans certaines conditions. C'est ce qui se passe lorsque l'on réalise une neurectomie vestibulaire unilatérale chez le chat adulte. Nos travaux révèlent en effet l'existence d'une neurogenèse réactionnelle dans les noyaux vestibulaires désafférentés situés dans le tronc cérébral. Plus étonnant encore, nous avons montré que cette prolifération cellulaire postlésionnelle était fonctionnelle et participait aux processus de restauration des fonctions posturolocomotrices. < SNC du mammifère adulte. Toutefois, à ce jour, seulement deux structures bien précises, la zone sous-granulaire du gyrus dentelé de l'hippocampe et la zone sous-ventriculaire qui borde les ventricules latéraux, renouvellent continuellement leur stock de neurones (Figure 1). Ces zones sont dites de neurogenèse car elles génèrent de nouveaux neurones [39]. La grande majorité d'entre eux survit et s'intègre ensuite dans des circuits neuronaux qui contribuent à la transmission de l'information dans le cerveau : tâches d'apprentissage, de mémorisation, d'orientation spatiale, ou encore de reconnaissance olfactive [1]. Par contraste, tout le reste du SNC est considéré comme étant non neurogène car les progéniteurs neuraux potentiellement présents sont maintenus dans un état de quiescence. L'environnement ne permet pas la prolifération, la survie et la différenciation cellulaires. Ainsi, des progéniteurs neuraux de la zone sous-granulaire ou de la zone sousventriculaire transplantés dans des zones non neurogènes meurent ou s'y différencient uniquement en cellules gliales [2][3][4]. En revanche, lorsque des progéniteurs provenant de n'importe quelle région du SNC sont transplantés dans des zones de neurogenèse, ils s'y différencient selon le type neuronal requis par le tissu hôte, neurones granulaires dans la zone sous-granulaire et interneurones dans la zone sous-ventriculaire [3][4][5][6]. Il apparaît donc que le devenir des progéniteurs neuraux au sein de leur tissu hôte est avant tout commandité par l'environnement extracellulaire, au détriment des paramètres intrinsèques aux cellules [7,8]. De manière intéressante, les influences qui semblent s'opposer à la neurogenèse dans la quasi-totalité du SNC pourraient être ponctuellement mises entre parenthèses dans certaines conditions. En effet, de nombreux travaux chez le mammifère adulte ont révélé que des pathologies particulières (ischémie, scléroses multiples, Le renouvellement des neurones dans le cerveau adulteAu même titre que les cellules intestinales ou sanguines, de nouveaux neurones sont capables d'être générés tout au long de la vie au sein de leur tissu d'appartenance. Ainsi, contrairement au dogme érigé en 1928 par Ramon y Cajal 1 : « Une fois le développement term...

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Effects of Chronic Infusion of a GABA_A Receptor Agonist or Antagonist into the Vestibular Nuclear Complex on Vestibular Compensation in the Guinea Pig

Cited by 15 publications

References 37 publications

Neurogenic Potential of the Vestibular Nuclei and Behavioural Recovery Time Course in the Adult Cat Are Governed by the Nature of the Vestibular Damage

Neurogenic Potential of the Vestibular Nuclei and Behavioural Recovery Time Course in the Adult Cat Are Governed by the Nature of the Vestibular Damage

Reactive Neurogenesis and Down-Regulation of the Potassium-Chloride Cotransporter KCC2 in the Cochlear Nuclei after Cochlear Deafferentation

Une nouvelle zone de neurogenèse fonctionnelle

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Effects of Chronic Infusion of a GABAA Receptor Agonist or Antagonist into the Vestibular Nuclear Complex on Vestibular Compensation in the Guinea Pig

Cited by 15 publications

References 37 publications

Neurogenic Potential of the Vestibular Nuclei and Behavioural Recovery Time Course in the Adult Cat Are Governed by the Nature of the Vestibular Damage

Neurogenic Potential of the Vestibular Nuclei and Behavioural Recovery Time Course in the Adult Cat Are Governed by the Nature of the Vestibular Damage

Reactive Neurogenesis and Down-Regulation of the Potassium-Chloride Cotransporter KCC2 in the Cochlear Nuclei after Cochlear Deafferentation

Une nouvelle zone de neurogenèse fonctionnelle

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Effects of Chronic Infusion of a GABA_A Receptor Agonist or Antagonist into the Vestibular Nuclear Complex on Vestibular Compensation in the Guinea Pig