Associate Professor, NeuRA
Conjoint Assoc Prof, Graduate School of Biomedical Engineering, UNSW
Adjunct Assoc Prof, School of Medicine, Johns Hopkins University, USA
+612 9399 1030
Assoc Prof Americo Migliaccio heads a research group that investigates the neural mechanisms underlying the vestibulo-ocular reflex (VOR). He is particularly focused on determining the neural mechanisms important for recovery after partial injury of the vestibular organ/s. He is also developing a new rehabilitation technique and device to modify VOR function.
DR SERAJUL KHAN Research Officer
ASSOC PROF MICHAEL SCHUBERT Honorary Senior Research Fellow
ASSOC PROF PHILLIP CREMER Honorary Senior Research Fellow
ASSOC PROF ALAN BRICHTA Honorary Senior Research Fellow
DR REBECCA LIM Honorary Research Fellow
CHRISTOPHER TODD Research Assistant
WILLIAM FIGTREE Research Assistant
TANVIR AHMED PhD student
MOHAMMED MAHFUZ PhD student
DAVID GRENET PhD student
CARLO RINAUDO PhD student
A visual stimulus driving the VOR gain to unity toward the nonadapting side aids unilateral adaptation more so than no visual stimulus.
Although anatomically well described, the functional role of the mammalian efferent vestibular system (EVS) remains unclear. Unlike in fish and reptiles, the mammalian EVS does not seem to play a role in modulation of primary afferent activity in anticipation of active head movements. However, it could play a role in modulating long-term mechanisms requiring plasticity such as vestibular adaptation. We measured the efficacy of vestibuloocular reflex (VOR) adaptation in α9-knockout mice. These mice carry a missense mutation of the gene encoding the α9 nicotinic acetylcholine receptor (nAChR) subunit. The α9 nAChR subunit is expressed in the vestibular and auditory periphery, and its loss of function could compromise peripheral input from the predominantly cholinergic EVS. We measured the VOR gain (eye velocity/head velocity) in 26 α9-knockout mice and 27 cba129 control mice. Mice were randomly assigned to one of three groups: gain-increase adaptation (1.5×), gain-decrease adaptation (0.5×), or no adaptation (baseline, 1×). After adaptation training (horizontal rotations at 0.5 Hz with peak velocity 20°/s), we measured the sinusoidal (0.2-10 Hz, 20-100°/s) and transient (1,500-6,000°/s(2)) VOR in complete darkness. α9-Knockout mice had significantly lower baseline gains compared with control mice. This difference increased with stimulus frequency (∼ 5% <1 Hz to ∼ 25% >1 Hz). Moreover, vestibular adaptation (difference in VOR gain of gain-increase and gain-decrease adaptation groups as % of gain increase) was significantly reduced in α9-knockout mice (17%) compared with control mice (53%), a reduction of ∼ 70%. Our results show that the loss of α9 nAChRs moderately affects the VOR but severely affects VOR adaptation, suggesting that the EVS plays a crucial role in vestibular plasticity.
We propose that impaired VORS and VM are because of similar, but distinct, consequences of selective partial cerebellar dysfunction. The patient's VORS data are consistent with a CANVAS neuropathological study showing selective degeneration of the dorsal vermis of the cerebellum, a region thought to be important for VORS. Taken together our findings suggest the patient is a CANVAS variant. We hypothesise VORS impairment is part of CANVAS, but not revealed because of vestibular loss.