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

Abstract

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.

Dissociation of doublecortin expression and neurogenesis in unipolar brush cells in the vestibulocerebellum and dorsal cochlear nucleus of the adult rat

“…These cells divide in response to injury (Nakagomi et al, 2009, Ohira et al, 2010, Nakagomi et al, 2011); reactive astrocytes in cortex may also proliferate in response to injury (Shimada et al, 2012). Similar cell populations in the brainstem and cerebellum could be the source of the reactive neurogenesis seen with vestibular damage (Tighilet et al, 2007, Dutheil et al, 2009, Dutheil et al, 2011b), and might be the source of the BrdU/Ki67-ir cells we see. However it is also possible that some or all of the cells we are labeling are non-neuronal.…”

“…12 in Manohar et al 2012). The idea of adult neurogenesis in the brainstem is supported by several studies that showed evidence of “reactive neurogenesis” in the brainstem following vestibular damage (Dutheil et al, 2009, Dutheil et al, 2011b, a). …”

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

“…Interestingly, this reactive neurogenesis played a critical role in restoring the vestibular function (Dutheil et al, 2009, 2011). This result suggests that newborn neurons can be integrated in a functional neural network and play an adaptive role in the vestibular recovery after peripheral damage.…”

Vestibular Lesion-Induced Developmental Plasticity in Spinal Locomotor Networks during Xenopus laevis Metamorphosis

“…In addition, a UL performed as early as stage 38 in Xenopus has been previously found to have no effect on the remaining pre-metamorphic development of the vestibular nuclei [39]. However, recent studies in the adult cat [40], [41] have reported that some neurogenesis, associated with behavioral recovery, can occur in vestibular nuclei in response to a unilateral vestibular neurectomy. Since neurogenesis is widespread in the larval anuran CNS and only ceases after metamorphosis [42], it is conceivable that such a latent developmental process occurring in the brainstem vestibular nuclei during metamorphosis somehow contributes to the locomotor recovery in post-metamorphic UL54 juveniles.…”