Vestibular animal models contributions to underst

Authors: Hans Straka Andreas Zwergal Kathleen E Cullen

Publish Date: 2016/04/15

Volume: 263, Issue: 1, Pages: 10-23

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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 Crossspecies comparisons have established that the morphophysiological 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 pathologiesScientific research on the vestibular system has benefitted from studies on a wide variety of vertebrate species 1 Systematic investigations of inner ear endorgans in fishes amphibians and birds performed over a century ago revealed many details of the structure/function of this sensory system and established that it is remarkably preserved across vertebrate phylogeny 2 3 This organizational conservation emphasizes that the ability to detect and encode body motion for gaze and posture stabilization as well as for orientation and navigation in space is essential across vertebrates 4 5 In addition the almost identical structure of sensory endorgans neuronal pathways and central circuits in different vertebrates provides the ability to make general conclusions regarding the signaling properties and computational capabilities of the neuronal components of vestibular pathways Moreover speciesspecific features related to different locomotor strategies/dynamics particular lifestyles or ecophysiological habitats offer the opportunity to evaluate the capacity of the system to adapt to new challenges Thus understanding the particularities and similarities of vestibular signal processing in different vertebrates have provided an essential opportunity to identify conceptual principles that coincide with the behavioral repertoire and performance This knowledge has in turn facilitated our understanding of the mechanistic operations required for stabilizing gaze and posture and yielded insight into substrates and processes underlying different pathologies and potential treatmentsNotably based on their evolutionary proximity to humans nonhuman primates have become a standard model for furthering our knowledge of basic vestibular processing and advancing translational research In addition advances in the generation of mouse lines with defined genetic backgrounds and/or transgenic lines such as CRE combined with viralbased optogenetics have provided new opportunities to probe the functional circuitry of vestibular pathways and gain insight into vestibular diseases or agerelated impairments 6 7 8 However it is also important to emphasize that work across a wider variety of different vertebrate models has improved our understanding of vestibular processing Research encompassing a combination of standard models and less widely used “exotic animals” with particular motion repertoires and/or unique experimental advantages have proven advantageous This review highlights recent progress that has been made toward understanding the fundamental physiological principles of vestibular processing using different animal models as well as how cellular and circuit properties are altered under pathophysiological conditionsThe vestibular endorgans are located within the petrosal bone in close vicinity to the cochlea This hidden location proximal to the auditory organ and the difficult access considerably delayed our understanding of the functional role of these inner ear organs It was only in 1824 that Flourens 9 conducted the first systematic behavioral studies on the vestibular system He discovered that interrupting specific semicircular canals in different vertebrate species including pigeons and rabbits produced directionspecific impairments of the equilibrium walking and head movements Interestingly he speculated that the deficits were due to changes in hearing sensitivity since the semicircular canals were then generally considered as part of the auditory organ In fact the vestibular system was only postulated to be a distinct sense independent of hearing in the late 19th century following systematic lesion experiments on frog pigeon 2 and dog 10 Both Goltz 2 and Bechterew 10 concluded that the semicircular canals were distinct organs responsible for posture and equilibrium in three spatial orientations This view was subsequently confirmed by studies in numerous other species including salamanders pigeons cockatoos and rabbits 3 Concurrently more theoretically based investigations determined that the semicircular canals sense head rotations 11 12 13As for the semicircular canals the initially assumed auditory role of otolith organs also remained unchallenged for a long time It is noteworthy that this historical progression in our understanding is reflected in existing terminology since otolith literally means “hearing stone” Theoretically based investigations had deduced that the otolith endorgans sense linear accelerations including head tilts 12 13 yet experimental work in fish found that removal of the large solid crystals otoconia covering the otolith sensory epithelia 14 significantly impaired their underwater hearing 15 Experiments in terrestrial vertebrates were required to definitively establish that the otolith organs are responsible for ensuring stable posture and equilibrium in landbased animals 3 16 This conclusion was then furthered by experiments in fish indicating that in this specific group of vertebrates the saccule/lagena may also serve as a hearing organ 17 thus exerting a dual functional roleIn summary a comparative approach including studies in vertebrate species from fish to mammals was essential to the progress that was made in the early vestibular research of the 19th century In particular the knowledge obtained following experimental lesions of semicircular canals otoliths and/or their nerves using different animal models has proven crucial for providing the important insight into speciesspecific adaptations of the endorgans and variations in their function relative to lifestyle ecophysiological niche or locomotor dynamicsHead motion relative to space is detected and decomposed into individual vector components by semicircular canal and otolith organs 18 The semicircular canals and otolith organs sense rotation and linear motion or changes in head position relative to the Earth´s gravitation vector respectively The fluidfilled ducts of the semicircular canals enable the detection of angular acceleration by means of the fluid’s inertia relative to sensory epithelia The mechanistic principle of the otolith organs is based on the inertia of an otolithic structure covering the sensory epithelia 19 While the spatial arrangement of the bilateral semicircular canals is largely conserved across vertebrates 20 comparative studies in fish frogs and birds demonstrate that otolith organs can serve an auditory as well as vestibular function as a result of differences in the morphophysiological properties of hair cells at a particular region of the otolithic epithelium 21 Thus in species such as frogs fish and likely also in mammals the otolith organs detect changes of the body position relative to the gravity vector as well as substrate/water vibrations 22 Furthermore the lagena an otolith organ that is present in all nonmammalian vertebrates and monotremes 23 likely contributes to the sense of magnetoreception that allows birds to make use of the geomagnetic field for orientation and navigation 24

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