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      Vestibular animal models: contributions to understanding physiology and disease

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          Abstract

          Our knowledge of the vestibular sensory system, its functional significance for gaze and posture stabilization, and its capability to ensure accurate spatial orientation perception and spatial navigation has greatly benefitted from experimental approaches using a variety of vertebrate species. This review summarizes the attempts to establish the roles of semicircular canal and otolith endorgans in these functions followed by an overview of the most relevant fields of vestibular research including major findings that have advanced our understanding of how this system exerts its influence on reflexive and cognitive challenges encountered during daily life. In particular, we highlight the contributions of different animal models and the advantage of using a comparative research approach. Cross-species comparisons have established that the morpho-physiological properties underlying vestibular signal processing are evolutionarily inherent, thereby disclosing general principles. Based on the documented success of this approach, we suggest that future research employing a balanced spectrum of standard animal models such as fish/frog, mouse and primate will optimize our progress in understanding vestibular processing in health and disease. Moreover, we propose that this should be further supplemented by research employing more “exotic” species that offer unique experimental access and/or have specific vestibular adaptations due to unusual locomotor capabilities or lifestyles. Taken together this strategy will expedite our understanding of the basic principles underlying vestibular computations to reveal relevant translational aspects. Accordingly, studies employing animal models are indispensible and even mandatory for the development of new treatments, medication and technical aids (implants) for patients with vestibular pathologies.

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          Most cited references147

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          The video head impulse test: diagnostic accuracy in peripheral vestibulopathy.

          The head impulse test (HIT) is a useful bedside test to identify peripheral vestibular deficits. However, such a deficit of the vestibulo-ocular reflex (VOR) may not be diagnosed because corrective saccades cannot always be detected by simple observation. The scleral search coil technique is the gold standard for HIT measurements, but it is not practical for routine testing or for acute patients, because they are required to wear an uncomfortable contact lens. To develop an easy-to-use video HIT system (vHIT) as a clinical tool for identifying peripheral vestibular deficits. To validate the diagnostic accuracy of vHIT by simultaneous measures with video and search coil recordings across healthy subjects and patients with a wide range of previously identified peripheral vestibular deficits. Horizontal HIT was recorded simultaneously with vHIT (250 Hz) and search coils (1,000 Hz) in 8 normal subjects, 6 patients with vestibular neuritis, 1 patient after unilateral intratympanic gentamicin, and 1 patient with bilateral gentamicin vestibulotoxicity. Simultaneous video and search coil recordings of eye movements were closely comparable (average concordance correlation coefficient r(c) = 0.930). Mean VOR gains measured with search coils and video were not significantly different in normal (p = 0.107) and patients (p = 0.073). With these groups, the sensitivity and specificity of both the reference and index test were 1.0 (95% confidence interval 0.69-1.0). vHIT measures detected both overt and covert saccades as accurately as coils. The video head impulse test is equivalent to search coils in identifying peripheral vestibular deficits but easier to use in clinics, even in patients with acute vestibular neuritis.
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            A clinical sign of canal paresis.

            Unilateral loss of horizontal semicircular canal function, termed canal paresis, is an important finding in dizzy patients. To our knowledge, apart from head-shaking nystagmus, no clinical sign of canal paresis has yet been described and the term derives from the characteristic finding on caloric tests: little or no nystagmus evoked by either hot or cold irrigation of the affected ear. We describe a simple and reliable clinical sign of total unilateral loss of horizontal semicircular canal function: one large or several small oppositely directed, compensatory, refixation saccades elicited by rapid horizontal head rotation toward the lesioned side. Using magnetic search coils to measure head and eye movement, we have validated this sign in 12 patients who had undergone unilateral vestibular neurectomy.
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              Vestibular system: the many facets of a multimodal sense.

              Elegant sensory structures in the inner ear have evolved to measure head motion. These vestibular receptors consist of highly conserved semicircular canals and otolith organs. Unlike other senses, vestibular information in the central nervous system becomes immediately multisensory and multimodal. There is no overt, readily recognizable conscious sensation from these organs, yet vestibular signals contribute to a surprising range of brain functions, from the most automatic reflexes to spatial perception and motor coordination. Critical to these diverse, multimodal functions are multiple computationally intriguing levels of processing. For example, the need for multisensory integration necessitates vestibular representations in multiple reference frames. Proprioceptive-vestibular interactions, coupled with corollary discharge of a motor plan, allow the brain to distinguish actively generated from passive head movements. Finally, nonlinear interactions between otolith and canal signals allow the vestibular system to function as an inertial sensor and contribute critically to both navigation and spatial orientation.
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                Author and article information

                Contributors
                straka@lmu.de
                Journal
                J Neurol
                J. Neurol
                Journal of Neurology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-5354
                1432-1459
                15 April 2016
                15 April 2016
                2016
                : 263
                : 10-23
                Affiliations
                [ ]Department Biology II, Ludwig-Maximilians-University Munich, Grosshaderner Str. 2, 82152 Planegg, Germany
                [ ]German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University of Munich, Munich, Germany
                [ ]Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, Germany
                [ ]Department of Physiology, McGill University, Montreal, QC H3A 0G4 Canada
                Article
                7909
                10.1007/s00415-015-7909-y
                4833800
                27083880
                dbfad0a3-8d8e-48e6-855f-abafc86948d9
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 5 August 2015
                : 11 September 2015
                : 12 September 2015
                Funding
                Funded by: German Federal Ministry of Education and Research
                Award ID: 01 EO 0901
                Award ID: 01 EO 0901
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000034, Institute of Neurosciences, Mental Health and Addiction (CA);
                Funded by: FundRef http://dx.doi.org/10.13039/100006955, Office of Extramural Research, National Institutes of Health (US);
                Award ID: DC002390
                Award Recipient :
                Categories
                Review
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2016

                Neurology
                otolith organ,semicircular canal,sensory–motor processing,motion perception,gaze stabilization,vestibulo-ocular reflex

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