AbstractsBiology & Animal Science

The neural mechanisms of vestibulo-ocular reflex plasticity

by Patrick Huebner

Institution: University of New South Wales
Department: Graduate School of Biomedical Engineering
Year: 2014
Keywords: VOR; Vestibular; Vestibulo-ocular reflex; Efferent; Mouse; Adaptation; Compensation; Plasticity; Glycine; Afferent
Record ID: 1073331
Full text PDF: http://handle.unsw.edu.au/1959.4/54246


The vestibular system possesses an extraordinary capacity for adaptation and compensation under normal and pathological conditions, respectively. These two forms of neural plasticity are essential for vestibular behaviours such as the vestibulo-ocular reflex (VOR). The VOR is responsible for maintaining a stable image on the retina by initiating compensatory eye movements in response to involuntary (passive) head perturbations. In order for this gaze stabilisation to be effective, the VOR pathways must be precisely calibrated. Remarkably, this reflex can adapt its sensitivity to head movements within seconds to account for changes in viewing conditions. Furthermore, within days it can compensate for changes in peripheral vestibular organ and optical plant function caused by, for example, development, ageing, illness or trauma. Recent behavioural and single-unit recording studies have suggested that tonic and phasic signal pathways under separate adaptive control, play an important role in mediating VOR adaptation and compensation. Precisely how these pathways contribute to vestibular plasticity has remained unknown. The objective of this thesis was to determine whether tonic and phasic vestibular signal pathways are involved in the neural mechanisms that drive VOR adaptation and compensation, and if these pathways are modulated through the efferent vestibular system (EVS). We tested the behavioural VOR using a high-speed whole-body mouse rotator to deliver vestibular stimuli, and video-oculography to measure the vestibular-evoked eye movement responses. In addition, we implemented a visual-vestibular mismatch adaptation training protocol that increased/decreased the VOR response. In study 1, the phasic pathway was studied using the SPD1/J mouse that has reduced glycine receptor sensitivity, one of the main inhibitory neurotransmitters of the phasic pathway. This neurotransmitter is thought to be involved in the communication between ipsilateral and contralateral vestibular nuclei of the brainstem, and in the communication between primary and second-order vestibular neurons and the cerebellum. Study 1 showed that despite this reduction in sensitivity, the phasic pathway recalibrated to produce a normal (slow-phase) VOR. Study 2 investigated the adaptive capacity of the tonic and phasic signal pathways. We showed that these pathways can be selectively adapted. Studies 3 and 4 considered the role of the mammalian EVS during VOR adaptation and compensation, respectively. Preliminary evidence suggested that EVS activity increases the contribution of the phasic pathway in order to boost vestibular plasticity. To test this, VOR plasticity of α9 knockout mice, a genetically modified strain with compromised EVS, was studied. Using these mice it was shown that a compromised EVS significantly impairs VOR plasticity. α9 knockout mice were unable to adapt their VOR response to visual-vestibular mismatch adaptation training (∼ 70 % reduction in adaptation capacity), and following unilateral vestibular lesion, showed only…