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HEARING AND LATERAL LINE | Vestibular System Anatomy and Physiology
Vestibular System Anatomy and Physiology H Straka, Ludwig-Maximilians-Universita¨t, Martinsried-Planegg, Germany R Baker, New York University Medical Center, New York, NY, USA ª 2011 Elsevier Inc. All rights reserved.
Introduction Organization of the Vestibular Sensory Periphery Central Location of Vestibular-Related Octavolateral Nuclei Origin of the Octavolateral Vestibular Subgroups Central Terminations of Semicircular Canal and Utricular Afferents Hindbrain Vestibuloocular Origins and Projections to Extraocular Motor Nuclei
Glossary Egocentric direction Navigation in space with a self-centered reference frame. Gaze stabilization Maintenance of stable eye and/or head position in respect to the environment. Gravitoinertial function Detection of static changes in head/body position relative to the Earth’s gravitation vector. Labyrinth A peripheral sensory compartment within the inner ear that includes semicircular canal and otolith end organs. Lagena An otolith end organ specialized, together with the sacculus, for detecting acoustic stimuli. Octavolateral nuclei Assembly of functional subgroups in the hindbrain that process sensory signals related to detection of water (lateral line) or object motion (electroreceptive), acoustic stimuli (hearing), or body motion (vestibular).
Introduction Vestibular neurons and circuits process information related to self-motion (i.e., head/body) in all vertebrates, including fish. The vestibular system is one component of a multisensory brainstem network because other sensory organs also detect self-motion (e.g., eyes and lateral line). Importantly, the most prominent signals triggering the motor behaviors essential for both escape and predation originate from sensory end organs in the inner ear. All fish use the vestibular system to transduce and then process information about their body position and motion in three-dimensional (3D) space, irrespective of either
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Horizontal Vestibuloocular Subgroups Vestibulospinal Projections for Locomotor Control and Posture Stabilization Auxiliary Vestibular Connections for Gaze and Posture Control Conservation of Fish Vestibular Organization in Other Vertebrates Further Reading
Otolith Solid calcium carbonate crystal in the saccule, lagena, and utricle, which are involved in the detection of vestibular and auditory stimuli. Otolith end organs Separate structures that contain sensory epithelia overlain by solid calcium carbonate crystals for detection of vestibular and auditory signals. Placode Region in the embryonic epithelial layer which gives rise to sensory organs and other structures. Sacculus An otolith end organ specialized, together with the lagena, for detecting acoustic stimuli. Semicircular canals Three interconnected membranous ducts within the inner ear that detect angular rotations during turning. Utricle An otolith end organ specialized for detecting both static and dynamic head motions. Vestibuloocular reflex Compensatory eye movements in response to vestibular stimulation that minimizes retinal slip to facilitate visual processing.
active or passive body movement arising from underwater currents. For a fish to maintain a particular posture in water, all motion-related sensory signals have to be trans formed within the central vestibular networks into motor commands appropriate for controlling the eyes, fins, body, and tail. The coordinated temporal and spatial activation of multiple and widely distributed appendages stabilize whole body position both at rest and during active swimming. As expected, all vertebrates are confronted with the effects of individual locomotor actions on their ability to perceive the surrounding environment. They must distin guish self from world/object motion. Self-generated as well
Hearing and Lateral Line | Vestibular System Anatomy and Physiology
as passive body motion cause retinal image displacements, with a resultant degradation in the processing of visual information. To maintain visual acuity, retinal image drift must be counteracted by dynamic (rapid) compensatory adjustments in eye position, largely provided by vestibu loocular reflexes (VORs). In essence, a fish must have precise knowledge about its body motion to maintain retinal constancy of objects in the environment by distin guishing whether the objects or their retinal locations are either stationary or moving. Achieving stable gaze with the VOR illustrates perfectly how the vestibular system func tions to enable continuous accurate perception of objects moving in the external world with respect to the self. Thus, the fact that the eyes are held still with respect to the environment under all conditions of body motion, especially independent of object motion, evolved many hundreds of millions of years ago by innovations in the hindbrain developing in parallel with cerebellar circuitry. Evolution also further utilized the vestibular system to compute the perceptual attribute commonly referred to as egocentric direction. Viewed from the context of motor control, a robust egocentric reference frame must exist in the hindbrain and cerebellar circuitry for an animal to choose an appropriate locomotor trajectory during swim ming. Thus, vestibular signals that originate from activation of the equilibrium organs in the inner ear during active and passive body motion play a crucial role in the ability to precisely perceive the environment and maintain appropri ate body position during locomotion. Perhaps the most significant vestibular attribute, therefore, is distinguishing self-motion from that of the world. Without doubt, vestib ular reflexes are essential for survival independent of the ecological niche, life style, and locomotor pattern of a particular species of fish. They allow a fish to distinguish self and self-motion from object motion in the world.
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The Ear and Hearing in Sharks, Skates, and Rays, and Psychoacoustics: What Fish Hear), and vestibular for body motion. The peripherally located epithelial end organs for these sensory modalities appear during early development from a common embryological region called the ‘placode’ (Figure 1). Individual placodal regions give rise either to lateral line/electroreceptive sensory struc tures on the body surface (AD, AV, M, P, and ST in Figure 1) or to inner ear vestibular/acoustic organs (OT in Figure 1). The sensory transduction mechanism in all cases is largely based on the same ancestral hair cell type (see also Hearing and Lateral Line: Auditory System Morphology). This ubiquitous mechanoreceptortype cell is used to detect and convert respective physical forces into neuronal activity, clearly distinguishing between electro- and mechano-sensory stimuli. Peripheral vestibular end organs of most fish consist of three separate semicircular canals attached to a single sac-like structure, the utriculus (fishes; Figure 2) (see also Hearing and Lateral Line: Auditory System Morphology). Two additional sac-like structures, the sac culus and the lagena, are largely utilized for hearing in nearly all fish species (see also Hearing and Lateral Line: The Ear and Hearing in Sharks, Skates, and Rays, Psychoacoustics: What Fish Hear, Physiology of the Ear and Brain: How Fish Hear, and Sound Source Localization and Directional Hearing in Fishes). Three semicircular canals are oriented at right angles from each other comprising three different planes, which likely offer the optimum physical arrangement for sensing 3D motion in a neutrally buoyant environment. Nevertheless, only one (hagfish; Figure 2) or two vertical canals (lampreys; Figure 2) were present in the most recent jawless fish ancestors; hence, the addition of a horizontal canal in Embryonic head placodes
Organization of the Vestibular Sensory Periphery Sensory signals related to body position and motion are processed and transformed into respective motor com mands in an assembly of hindbrain neuronal subgroups, collectively described in the literature as the octavolateral nuclei (see also Hearing and Lateral Line: Auditory/ Lateral Line CNS: Anatomy). Functionally, these hetero geneous subgroups of neurons process four different sensory modalities: lateral line for detection of either water motion (mechanoreceptive) (see also Hearing and Lateral Line: Lateral Line Structure and Lateral Line Neuroethology) or objects (electroreceptive) (see also Detection and Generation of Electric Signals: Detection and Generation of Electric Signals in Fishes: An Introduction), auditory for acoustic stimuli (see also Hearing and Lateral Line: Auditory System Morphology,
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Figure 1 Ontogenetic origin of mechanoreceptive sensory organs (lateral line, electroreception, inner ear vestibular, and auditory sensation). Schematic side view of a fish embryo depicting common placodal origins. AD, anterodorsal placode; AV, anteroventral placode; M, middle placode; OT, otic placode; P, posterior placode; ST, supratemporal placode.
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Figure 2 Phylogeny of vestibular labyrinths. A single semicircular canal with two patches (a, p) of sensory epithelia for sensing both anterior (A) and posterior (P) motion (hagfish). Separate anterior (A) and posterior (P) semicircular canal with specialized (a, p) sensory epithelia are found in jawless fish (lamprey). A common central macular organ (CM) is present for graviception in both species. In elasmobranchs and bony fishes, two vertical (A, P) and one horizontal (H) semicircular canal are oriented perpendicular to each other for detection of 3D angular acceleration by cupular deflections (a, p, h). Three separate macula organs (U, L, and S) serve as graviceptive (utricle) and pressure-detecting sensors (lagena, saccule).
elasmobranchs and bony fish arose as a new invention during fish evolution. This newly acquired mirror-image arrangement of the sensory periphery (fishes; Figure 2) is a major structural design of the vestibular system that allows the semicircular canals and the utricle to act reci procally during head motion. The semicircular canals, as well as the otolith organs (utricle, sacculus, and lagena), are filled with endolymph, a potassium-rich fluid that plays an essential role in the sensory signal transduction process. Each canal has an expansion known as an ‘ampulla’ containing a crista, cov ered by a gelatinous cupula, which is deformed by fluid movements during head/body motion. The canals detect turning movements of the head/body about their respective axis (Figure 2), thus acting as force transducers of angular acceleration. The utricle contains a single calcium carbo nate stone, called an ‘otolith’, overlying a fixed macula of hair cells and this organization is highly effective for trans ducing linear acceleration. The presence of single otolithic masses in teleosts is the reason for initially referring to these sensory structures as otolith organs (see also Hearing and Lateral Line: Auditory System Morphology). The major role of the utricle in fish relates to sensing inertia through detection of static changes in head/body position relative to the Earth’s gravitation vector, thereby creating an internal frame of reference for establishing egocentric direction responsible for orientation and locomotor behaviors. These major utricular roles observed in fish fit well with an earlier evolutionary appearance of this end organ than that of the semicircular canals, which require a critical spatial dimension to allow fluid movements for the detec tion of head motion. For this reason, it seems inappropriate to call the peripheral vestibular end organs simply the inner ear (see also Hearing and Lateral Line: Biomechanics of the Inner Ear in Fishes). Peripheral hair cells in both the lateral line/electro sensory neuromasts on the body surface as well as the specialized vestibular/auditory end organs in the inner ear are chemically linked to first-order afferent nerve
fibers that forward the sensory signals to distinct nuclear regions in the dorsal hindbrain. Vestibular afferent fibers that innervate the different semicircular canal organs and utricle are segregated from all other VIIIth nerve compo nents. In addition, vestibular afferents project exclusively to the most lateral octavolateral subgroups in the hind brain. Based on an evolutionarily conserved neuronal projection to brainstem and spinal regions, largely responsible for the control of balance and locomotion, the lateral portions of the octavolateral nuclei can be distinguished from the more medial and dorsal nuclei that process acoustic and lateral line sensory signals (Figure 3).
Central Location of Vestibular-Related Octavolateral Nuclei The vestibular nuclei occupy a considerable part of the dorso-lateral hindbrain between the Vth and Xth cranial nerves (Figure 3) (see also Hearing and Lateral Line: Auditory/Lateral Line CNS: Anatomy). Comparison of morphological features in several species of fish generally identifies five major subdivisions of second-order neurons in the vestibular nuclei. Moreover, distinct functional groups, identified according to their neuronal signals, are associated with a particular behavior (e.g., eye or body motion) and correlate reasonably well with the anatomical map. The similarity of structure and function of the major vestibular cell groups that control eye, fin, body, and tail motion across different fish species, therefore, allows vesti buloocular, vestibulospinal, vestibulocommissural, and vestibulocerebellar neurons to be identified as distinct populations. By and large, the current delineation of ves tibular subgroups is based on: (1) regionally restricted terminations of first-order afferent fibers from the different peripheral vestibular end organs; (2) anatomical tract tracing from efferent projection areas in the midbrain, hindbrain, and spinal cord; and (3) electrophysiological
Hearing and Lateral Line | Vestibular System Anatomy and Physiology (a)
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Figure 3 Spatial arrangement of goldfish octavolateral vestibular nuclei. Schematic sagittal (a) and coronal (b) diagrams depicting the location of brainstem nuclei. Arrow with dashed line in the sagittal view indicates the level of the coronal section. Abd, abducens motor nucleus; AO, DO, MO, PO, anterior, descending, medial, posterior octavolateral nuclei; CC, crus cerebelli; GT, gustatory tract; IIIn, VIIn, VIIIn, IXn, Xn, and Vn, oculomotor, facial, vestibular, glossopharyngeal, vagal, trigeminal nerves; MAN, medial auditory nucleus; MLF, medial longitudinal fasciculus; MED, medial nucleus; PLL, posterior lateral line nucleus; Ret, reticular formation; T, tangential nucleus.
correlates of second-order neurons during different beha vioral paradigms. The most comprehensive topographical mapping and electrophysiological studies have been car ried out in goldfish (Carassius auratus), and this species is used here as an example to summarize the overall organization of the vestibular subgroups within the octa volateral nuclei.
Origin of the Octavolateral Vestibular Subgroups All vestibular subgroups take their origin from a hindbrain segmental framework, which begins in early development as eight well-defined neuroepithelial compartments. The early embryonic hindbrain patterning serves as a mechan istic guide that directs the development of particular vestibular functional phenotypes involved in stabilization of retinal images and body posture. Combinatorial expres sion of spatially restricted regulatory genes plays a dominant patterning role in the development of any neu ron, vestibuloocular, or vestibulospinal, in any of the eight hindbrain compartments. This genetically specified com partmental blueprint is conserved between all species of fish, as well as for subsequent terrestrial vertebrates with only minor modifications. Vestibular neuronal subgroups evolved long before modern fishes in the earliest and now-extinct groups of jawless vertebrates. Interestingly, in living lampreys, the two vertically oriented semicircular canals, anterior and posterior (Figure 2), contribute equally to detection of the horizontal components of angular head acceleration. Hence, there are two well-delineated horizontal vestib ular subgroups in the hindbrain. However, a third (horizontal) canal was added to the ontogenetic blue print in modern sharks and fishes (Figure 2) such that
the two separate horizontal vestibular subgroups receive a common afferent input from one canal rather than a separate signal from the original anterior and posterior canal design. Notably, this structural design of two sepa rate horizontal vestibular subgroups, unique to central horizontal eye movement circuitry, has been conserved ever since it evolved in jawless fishes to present-day mammals. Ever since the earliest jawless vertebrates, the vesti bular subgroups appear to align with the peripheral location of the anterior and posterior semicircular canals surrounding a central otolith. However, such a stereo typed arrangement is more apparent than real because first-order vestibular afferents exhibit the capability to contact neurons in any of the vestibular subnuclei. Thus, it is likely that the vestibular system in jawless and jawed fishes was quickly converted from a point-to-point, hardwired canal/otolith projection to a highly integrated net work in which the appropriate vestibular signal could be utilized independent of the canal of origin but more dependent on the functional role of the targeted motor circuit. The primitive vestibular system largely relayed purely sensory signals to subsets of neurons that effectively could both generate and relay online signals to motor nuclei. However, in most cases, the vestibular signal can be equally correlated with the sensory stimulus (head motion) or the motor response (eye motion). It turns out that, quite early in evolution, fishes had converted the sensory-related neural activity in many of their vestibular subgroups into motor coordinates (e.g., as seen in goldfish second-order neurons) that exhibit all of the horizontal eye movement signals for visuo-vestibular-induced eye movements. From a systems control point of view, the vestibular subgroups are much more than simple sensory relay neurons; they also represent the motor command
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for appropriate contractions of eye, fin, body, and tail muscles.
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Central Terminations of Semicircular Canal and Utricular Afferents The distribution of first-order afferent fibers from indivi dual canals and the utricle allows individual vestibular nuclei to be recognized with respect to the direction of head/body motion. Anterior and posterior canal afferents terminate predominantly, though not exclusively, in the anterior octavolateral nucleus (AO) and the tangential nucleus (T) (Figure 3). Afferent projections from these two canals are less dense in the descending octavolateral nucleus (DO) and the posterior octavolateral nucleus (PO) (Figure 3). In contrast, the horizontal canal afferent termination coincides with one set of smaller neurons in the magnocellular octavolateral nucleus (MO), as well as more uniformly in another subset located throughout DO and T (Figure 3). First-order utricular afferents termi nate predominantly in MO, T, and DO, thus overlapping to a considerable extent with those from the horizontal canal. Significant for all sensorimotor behaviors in fish, there are virtually no vestibular nuclei that receive exclu sive afferent projections from a single peripheral end organ. Rather, first-order afferents overlap more or less completely, even though hot spots of terminations of fibers from particular vestibular organs exist in some nuclei. This widespread vestibular afferent pattern thus differs from topological maps of other sensory systems such as the closely related visual system. The absence of a sensory point-to-point map is consistent with the finding that signal processing in central vestibular nuclei is spa tially organized more according to efferent (largely motor) targets rather than topological hindbrain location. Observations on the distribution of afferent inputs are, in turn, quite compatible with the demonstrated roles of the vestibular subgroups in sensorimotor transformations contributing to the control of gaze (eye/head) and posture.
Hindbrain Vestibuloocular Origins and Projections to Extraocular Motor Nuclei Perhaps the dominant structural attribute of the vesti bular system is the spatially precise projection of vestibular subgroups to extraocular motoneurons located in the oculomotor, trochlear, and abducens nuclei. These three-neuronal VOR pathways consisting of first- and second-order vestibular and extraocular motoneurons are responsible for compensatory, 3D eye movements in all species of fish. Continuous, unblurred
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PC Figure 4 Extraocular muscles and pulling directions (view from dorsal) are illustrated with respect to semicircular canal orientation. Horizontal (HC, red), anterior (AC, green), and posterior vertical canal (PC, blue) are aligned with matching pairs of synergistic ipsi- and contralateral eye muscles (see matching color codes). LR, MR, lateral, medial rectus; IO, SO, inferior, superior rectus; IR, SR, inferior, superior rectus.
vision during high frequency and large amplitudes of head motion would not be possible without the vestibu lar nuclei. Compensatory eye movements are produced in fish, as in all other vertebrates, by a set of six eye muscles that insert on each eye bulb, such that any horizontal, verti cal, or torsional movement can be performed (Figure 4). A major organizational principle of the angular VOR is the approximate alignment of the axes of a particular semicircular canal and the pulling directions of syner gistic sets of two extraocular muscles (Figure 4). This arrangement illustrates the intricate link that has evolved between sensory and extraocular reference frames that in many species nearly perfectly stabilizes vision in response to eye/head body motion. The ves tibular neuronal subgroups critical for sensorimotor transformation of angular as well as linear acceleration signals are located laterally within the borders of AO and DO/PO (Figure 3). In general terms, the fundamental rule underlying any vestibuloocular connection is matching the spatial vector orientations for body movements around the roll and pitch axes with the extraocular motoneurons producing vertical and tor sional eye movements. Afferent input from the two vertical canals comprises the major input for vestibular subgroups activating extraocular muscles (SR, IR, SO, and IO) with corresponding spatially aligned pulling directions (Figure 4). Second-order vestibular neurons form behaviorally different and spatially nonoverlapping subgroups
Hearing and Lateral Line | Vestibular System Anatomy and Physiology
within the vestibular portion of the octavolateral nuclei. The functionally distinguishable oculomotor/ trochlear-projecting vestibuloocular neurons originate mainly from a rostral (AO) and to a minor extent from a caudal vestibular area (DO/PO). Each respective subgroup of vestibuloocular neurons receives afferent labyrinthine input from either the anterior or posterior vertical semicircular canal compatible with the spatial specificity of their target vertical and oblique extraocular motoneurons (SO, IO, SR, and IR). An additional organizational principle of the vestibulomo tor projections is a push–pull arrangement that allows excitation of particular sets of eye muscles and simul taneous inhibition of the respective sets of antagonists. Accordingly, vestibuloocular projections consist of inhibitory neurons, whose axons remain ipsilateral, and excitatory neurons, whose axons cross the midline
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to match agonist/antagonistic extraocular motor tar gets. Axons from the excitatory and inhibitory vestibuloocular subgroups reach their respective sub divisions in the oculomotor/trochlear nuclei by pathways in the ipsi- or contralateral medial longitu dinal fasciculus (MLF) (Figure 3).
Horizontal Vestibuloocular Subgroups Horizontal eye movements (upper panel in Figure 5) are particularly important for scanning the visual horizon and both eyes move conjointly producing conjugate movements that together encompass a much larger oculomotor range. However, conjugacy of eye movements in fish is much more apparent than real because a fovea is absent and the fusion of targets between the two eyes (stereoscopic vision) is
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Figure 5 Brainstem circuitry and compensatory conjugate horizontal angular vestibuloocular reflexes. Both right (blue) and left (red) eye motion are equal and opposite to horizontal head rotation as illustrated best by the eye vs. head velocity traces. A simplified view of the brainstem vestibuloocular pathways is shown in the lower schematic.
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limited, if present at all. The classical push–pull organiza tion present for vertical eye movements with a nearly mirror-symmetrical, crossed excitation, and an uncrossed inhibition is only established for abducens motoneurons that innervate the ipsilateral lateral rectus (LR) muscle and internuclear neurons that innervate the contralateral medial rectus (MR; Figure 5). There is no direct uncrossed vestibular inhibition of MR motoneurons because internuc lear neurons receive the same vestibular inhibitory input as LR motoneurons. This intrinsic difference in organization likely facilitates an independent bilateral activation of MR motoneurons for converging eye movements without activation of the LR motoneurons and vice versa for con vergence and divergence eye movements. The principal vestibular subgroups implicated in the horizontal VOR conveying a dynamic head/eye velocity signal are located in the ventral part of DO with projections to four separate, ventrally located, subgroups of abducens (Abd) motoneurons and internuclear (AI) neurons (simpli fied view with single subgroups in Figure 5). A subgroup of horizontal head velocity neurons is located in the rostral MO that project exclusively to ipsilateral MR motoneur ons. While the head velocity signal on AI and MO subpopulations might be considered as redundant, it likely is not, because the MO neurons subserve an essential highfrequency vestibular role not provided by AI neurons. In addition, this vestibular subgroup is maintained in mam mals, giving rise to a well-delineated pathway (ascending tract of Deiter’s) to the oculomotor nucleus. The highly conserved locations of horizontal canal-related, secondorder vestibuloocular neurons within the vertebrate hind brain clearly indicate an organizational principle centered on motor coordinates rather than topography of spatially segregated inputs from the sensory periphery. Both vertical and horizontal canal-related vestibulo ocular neurons are complemented by a densely clustered subgroup that forms the T nucleus just caudal to the VIIIth nerve entry (Figure 3). The functional role of this nucleus is clearly demonstrated by the close relationship between torsional angle of the eye and head tilt that appears even in larval fish before semicircular canals become operational. This nucleus serves as a gravito inertial center with crossed excitatory projections to the midbrain oculomotor/trochlear nuclei and the contra lateral spinal cord. Second-order vestibular neurons in the tangential nucleus receive major inputs from the utricle as well as minor inputs from the three canals in a spatially specific pattern. In contrast to vestibular neu rons in the semicircular canal-specific nuclei, tangential neurons exhibit a sustained sensitivity after small tonic changes of the head position, clearly indicating an appreciable tonic utricular influence. The likely conver gence of spatially specific afferent canal inputs with sensory signals from utricular sectors with the same spatial vector orientation in individual tangential
neurons forms a structural substrate that makes this nucleus a gravitoinertial relay center for vestibuloocular as well as postural reflexes.
Vestibulospinal Projections for Locomotor Control and Posture Stabilization Vestibulospinal projections control gravitoinertial-related postural reflexes through the activation of spinal inter neurons and motoneurons. Vestibular signals to spinal targets exhibit either low dynamics that are more corre lated with changes in body posture, or high dynamics that are involved in the initiation of fast locomotor actions. Vestibulospinal neurons are generally well localized within a restricted region that coincides with a central position along the rostro-caudal extent of the vestibular areas in the octavolateral nuclei. This central location within the vestibular column is compatible with an early evolutionary appearance of gravitoinertial function utiliz ing utricular signals for compensating pitch and roll deviations of body position in space. The populations of ipsi- and contralaterally descending vestibulospinal neu rons largely located in MO and the dorsal part of DO are morphologically heterogeneous and convey otolith as well as semicircular canal signals to the spinal cord. A number of vestibulospinal neurons are also located in the T nucleus intermingled with those that project to the contralateral oculomotor/trochlear nuclei, suggesting that this nucleus serves as a gravitoinertial relay center coupling eye motion and body posture control.
Auxiliary Vestibular Connections for Gaze and Posture Control Commissural projections through midline crossing axons interconnect bilateral vestibular nuclei. Functionally, the spatially specific inhibitory brainstem commissural pro jections that interconnect vestibular neurons with bilateral coplanar canal-related signals (e.g., ipsilateral posterior–contralateral anterior; see Figure 4) reinforce the differential detection of angular head acceleration signals due to the mirror-image arrangement of the semi circular canals in the periphery on both sides. This connection increases the sensitivity for detection of angu lar head acceleration, such that very small signals can be distinguished. A somewhat similar organization exists for utricular commissural connections that link second-order vestibular neurons with signals from spatially aligned bilateral utricular epithelial sectors. However, the specific functional interconnections are more complex given the 360� response sensitivity of the sensory epithelium on each side. Vestibular commissural neurons that
Hearing and Lateral Line | Vestibular System Anatomy and Physiology
interconnect the two sides essentially subdivide into ros tral and caudal subgroups in the AO and DO/PO, respectively. Given the dense projection and termination of anterior and posterior semicircular canal afferent fibers in AO, DO, and PO regions where commissural neurons are located, these latter cell groups likely establish a push–pull connectivity to increase the sensitivity for detection of vertical coplanar semicircular canal signals. Vestibular projections to the vestibulolateral lobe of the cerebellum in fish play an important role in the adaptation and plasticity of gaze-stabilizing reflexes. These connections are evolutionarily very old and are based on an intimate phylogenetic linkage between the octavolateral nuclei and cerebellum. Both, first- and second-order vestibular projections, convey angular head/body acceleration as mossy fiber input to the gran ular layer of the vestibulocerebellum. In turn, Purkinje cells from the caudal lobe of the vestibulocerebellum provide a direct output to particular vestibuloocular sub groups. The major locations for vestibulocerebellar projection neurons are a rostral subgroup with ipsilateral projection predominance in AO and a second one in DO/PO. The caudal vestibular subpopulation is contig uous with another population of cerebellar-projecting neurons located ventrolaterally in the caudal hindbrain. Together, along with cerebellar-projecting inferior oli vary neurons, these populations appear to have a common ontogenetic origin, such that all precerebellar nuclei responsible for eye/head motion derive from a common caudal hindbrain region.
Conservation of Fish Vestibular Organization in Other Vertebrates Comparison of the spatial distribution of individual vestib ular end-organ terminations among different groups of fish, such as damselfish, goby, toadfish, and elasmobranchs, reveals a vestibular pattern similar to that in goldfish. Notably, central projections from comparable populations of vestibular neurons originate from corresponding sub divisions, even though specific morphological details, particularly size, differ between the various species. This conservation also includes connectivity with particular targets, even in the exceptional case of flatfish, where both peripheral and central structural rearrangements occur during development. A comparison of vestibular system anatomy and physiology of fish with tetrapods also reveals a remarkably conserved pattern. In fact, affer ent projections from the different vestibular end organs in all tetrapod taxa terminate differentially in areas that cor respond to those in fish. Moreover, similar subgroups of major vestibular projection neurons originate from homo logous positions in the hindbrain of mammals, birds,
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and amphibians. These comparative attributes suggest that, from basic wiring through function, the vestibular blueprint was established quite early during vertebrate evolution and has been largely conserved unchanged throughout 400 million years of vertebrate phylogeny. See also: Detection and Generation of Electric Signals: Detection and Generation of Electric Signals in Fishes: An Introduction. Hearing and Lateral Line: Auditory/Lateral Line CNS: Anatomy; Auditory System Morphology; Lateral Line Neuroethology; Lateral Line Structure; Psychoacoustics: What Fish Hear; The Ear and Hearing in Sharks, Skates, and Rays.
Further Reading Gibbs MA and Northcutt RG (2004) Development of the lateral line system in the shovelnose sturgeon. Brain Behavior and Evolution 64: 70–84. Graf W and Baker R (1983) Adaptive changes of the vestibulo-ocular reflex in flatfish are achieved by reorganization of central nervous pathways. Science 221: 777–779. Graf W and Baker R (1985) The vestibuloocular reflex of the adult flatfish. II. Vestibulooculomotor connectivity. Journal of Neurophysiology 54: 900–916. Graf W, Spencer R, Baker H, and Baker R (1997) Excitatory and inhibitory vestibular pathways to the extraocular motor nuclei in goldfish. Journal of Neurophysiology 77: 2765–2779. Highstein SM, Kitch R, Carey J, and Baker R (1992) Anatomical organization of the brainstem octavolateralis area of the oyster toadfish, Opsanus tau. Journal of Comparative Neurology 319: 501–518. Maruska KP and Tricas TC (2009) Central projections of octavolateralis nerves in the brain of a soniferous damselfish (Abudefduf abdominalis). Journal of Comparative Neurology 512: 628–650. McCormick CA and Braford MR, Jr. (1994) Organization of inner ear endorgan projections in the goldfish, Carassius auratus. Brain Behavior and Evolution 43: 189–205. McCormick CA and Hernandez DV (1996) Connections of octaval and lateral line nuclei of the medulla in the goldfish, including the cytoarchitecture of the secondary octaval population in goldfish and catfish. Brain Behavior and Evolution 47: 113–137. McElligott JG, Beeton P, and Polk J (1998) Effect of cerebellar inactivation by lidocaine microdialysis on the vestibuloocular reflex in goldfish. Journal of Neurophysiology 79: 1286–1294. Pastor AM, De la Cruz RR, and Baker R (1994) Eye position and eye velocity integrators reside in separate brainstem nuclei. Proceedings of National Academy of Sciences of the United States of America 91: 807–811. Pastor AM, De la Cruz RR, and Baker R (1997) Characterization of Purkinje cells in the goldfish cerebellum during eye movement and adaptive modification of the vestibulo-ocular reflex. Progress in Brain Research 114: 359–381. Pastor AM, Torres B, Delgado-Garcia JM, and Baker R (1991) Discharge characteristics of medial rectus and abducens motoneurons in the goldfish. Journal of Neurophysiology 66: 2125–2140. Straka H and Dieringer N (2004) Basic organization principles of the VOR: Lessons from frogs. Progress in Neurobiology 73: 259–309. Suwa H, Gilland E, and Baker R (1996) Segmental organization of vestibular and reticular projections to spinal and oculomotor nuclei in the zebrafish and goldfish. Biological Bulletin 191: 257–259. Suwa H, Gilland E, and Baker R (1999) Otolith ocular reflex function of the tangential nucleus in teleost fish. Annals of the New York Academy of Sciences 871: 1–14. Tomchik SM and Lu Z (2005) Octavolateral projections and organization in the medulla of a teleost fish, the sleeper goby (Dormitator latifrons). Journal of Comparative Neurology 481: 96–117.
Introduction Organization of the Vestibular Sensory Periphery Central Location of Vestibular-Related Octavolateral Nuclei Origin of the Octavolateral Vestibular Subgroups Central Terminations of Semicircular Canal and Utricular Afferents Hindbrain Vestibuloocular Origins and Projections to Extraocular Motor Nuclei
Glossary Egocentric direction Navigation in space with a self-centered reference frame. Gaze stabilization Maintenance of stable eye and/or head position in respect to the environment. Gravitoinertial function Detection of static changes in head/body position relative to the Earth’s gravitation vector. Labyrinth A peripheral sensory compartment within the inner ear that includes semicircular canal and otolith end organs. Lagena An otolith end organ specialized, together with the sacculus, for detecting acoustic stimuli. Octavolateral nuclei Assembly of functional subgroups in the hindbrain that process sensory signals related to detection of water (lateral line) or object motion (electroreceptive), acoustic stimuli (hearing), or body motion (vestibular).
Introduction Vestibular neurons and circuits process information related to self-motion (i.e., head/body) in all vertebrates, including fish. The vestibular system is one component of a multisensory brainstem network because other sensory organs also detect self-motion (e.g., eyes and lateral line). Importantly, the most prominent signals triggering the motor behaviors essential for both escape and predation originate from sensory end organs in the inner ear. All fish use the vestibular system to transduce and then process information about their body position and motion in three-dimensional (3D) space, irrespective of either
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Horizontal Vestibuloocular Subgroups Vestibulospinal Projections for Locomotor Control and Posture Stabilization Auxiliary Vestibular Connections for Gaze and Posture Control Conservation of Fish Vestibular Organization in Other Vertebrates Further Reading
Otolith Solid calcium carbonate crystal in the saccule, lagena, and utricle, which are involved in the detection of vestibular and auditory stimuli. Otolith end organs Separate structures that contain sensory epithelia overlain by solid calcium carbonate crystals for detection of vestibular and auditory signals. Placode Region in the embryonic epithelial layer which gives rise to sensory organs and other structures. Sacculus An otolith end organ specialized, together with the lagena, for detecting acoustic stimuli. Semicircular canals Three interconnected membranous ducts within the inner ear that detect angular rotations during turning. Utricle An otolith end organ specialized for detecting both static and dynamic head motions. Vestibuloocular reflex Compensatory eye movements in response to vestibular stimulation that minimizes retinal slip to facilitate visual processing.
active or passive body movement arising from underwater currents. For a fish to maintain a particular posture in water, all motion-related sensory signals have to be trans formed within the central vestibular networks into motor commands appropriate for controlling the eyes, fins, body, and tail. The coordinated temporal and spatial activation of multiple and widely distributed appendages stabilize whole body position both at rest and during active swimming. As expected, all vertebrates are confronted with the effects of individual locomotor actions on their ability to perceive the surrounding environment. They must distin guish self from world/object motion. Self-generated as well
Hearing and Lateral Line | Vestibular System Anatomy and Physiology
as passive body motion cause retinal image displacements, with a resultant degradation in the processing of visual information. To maintain visual acuity, retinal image drift must be counteracted by dynamic (rapid) compensatory adjustments in eye position, largely provided by vestibu loocular reflexes (VORs). In essence, a fish must have precise knowledge about its body motion to maintain retinal constancy of objects in the environment by distin guishing whether the objects or their retinal locations are either stationary or moving. Achieving stable gaze with the VOR illustrates perfectly how the vestibular system func tions to enable continuous accurate perception of objects moving in the external world with respect to the self. Thus, the fact that the eyes are held still with respect to the environment under all conditions of body motion, especially independent of object motion, evolved many hundreds of millions of years ago by innovations in the hindbrain developing in parallel with cerebellar circuitry. Evolution also further utilized the vestibular system to compute the perceptual attribute commonly referred to as egocentric direction. Viewed from the context of motor control, a robust egocentric reference frame must exist in the hindbrain and cerebellar circuitry for an animal to choose an appropriate locomotor trajectory during swim ming. Thus, vestibular signals that originate from activation of the equilibrium organs in the inner ear during active and passive body motion play a crucial role in the ability to precisely perceive the environment and maintain appropri ate body position during locomotion. Perhaps the most significant vestibular attribute, therefore, is distinguishing self-motion from that of the world. Without doubt, vestib ular reflexes are essential for survival independent of the ecological niche, life style, and locomotor pattern of a particular species of fish. They allow a fish to distinguish self and self-motion from object motion in the world.
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The Ear and Hearing in Sharks, Skates, and Rays, and Psychoacoustics: What Fish Hear), and vestibular for body motion. The peripherally located epithelial end organs for these sensory modalities appear during early development from a common embryological region called the ‘placode’ (Figure 1). Individual placodal regions give rise either to lateral line/electroreceptive sensory struc tures on the body surface (AD, AV, M, P, and ST in Figure 1) or to inner ear vestibular/acoustic organs (OT in Figure 1). The sensory transduction mechanism in all cases is largely based on the same ancestral hair cell type (see also Hearing and Lateral Line: Auditory System Morphology). This ubiquitous mechanoreceptortype cell is used to detect and convert respective physical forces into neuronal activity, clearly distinguishing between electro- and mechano-sensory stimuli. Peripheral vestibular end organs of most fish consist of three separate semicircular canals attached to a single sac-like structure, the utriculus (fishes; Figure 2) (see also Hearing and Lateral Line: Auditory System Morphology). Two additional sac-like structures, the sac culus and the lagena, are largely utilized for hearing in nearly all fish species (see also Hearing and Lateral Line: The Ear and Hearing in Sharks, Skates, and Rays, Psychoacoustics: What Fish Hear, Physiology of the Ear and Brain: How Fish Hear, and Sound Source Localization and Directional Hearing in Fishes). Three semicircular canals are oriented at right angles from each other comprising three different planes, which likely offer the optimum physical arrangement for sensing 3D motion in a neutrally buoyant environment. Nevertheless, only one (hagfish; Figure 2) or two vertical canals (lampreys; Figure 2) were present in the most recent jawless fish ancestors; hence, the addition of a horizontal canal in Embryonic head placodes
Organization of the Vestibular Sensory Periphery Sensory signals related to body position and motion are processed and transformed into respective motor com mands in an assembly of hindbrain neuronal subgroups, collectively described in the literature as the octavolateral nuclei (see also Hearing and Lateral Line: Auditory/ Lateral Line CNS: Anatomy). Functionally, these hetero geneous subgroups of neurons process four different sensory modalities: lateral line for detection of either water motion (mechanoreceptive) (see also Hearing and Lateral Line: Lateral Line Structure and Lateral Line Neuroethology) or objects (electroreceptive) (see also Detection and Generation of Electric Signals: Detection and Generation of Electric Signals in Fishes: An Introduction), auditory for acoustic stimuli (see also Hearing and Lateral Line: Auditory System Morphology,
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Figure 1 Ontogenetic origin of mechanoreceptive sensory organs (lateral line, electroreception, inner ear vestibular, and auditory sensation). Schematic side view of a fish embryo depicting common placodal origins. AD, anterodorsal placode; AV, anteroventral placode; M, middle placode; OT, otic placode; P, posterior placode; ST, supratemporal placode.
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Figure 2 Phylogeny of vestibular labyrinths. A single semicircular canal with two patches (a, p) of sensory epithelia for sensing both anterior (A) and posterior (P) motion (hagfish). Separate anterior (A) and posterior (P) semicircular canal with specialized (a, p) sensory epithelia are found in jawless fish (lamprey). A common central macular organ (CM) is present for graviception in both species. In elasmobranchs and bony fishes, two vertical (A, P) and one horizontal (H) semicircular canal are oriented perpendicular to each other for detection of 3D angular acceleration by cupular deflections (a, p, h). Three separate macula organs (U, L, and S) serve as graviceptive (utricle) and pressure-detecting sensors (lagena, saccule).
elasmobranchs and bony fish arose as a new invention during fish evolution. This newly acquired mirror-image arrangement of the sensory periphery (fishes; Figure 2) is a major structural design of the vestibular system that allows the semicircular canals and the utricle to act reci procally during head motion. The semicircular canals, as well as the otolith organs (utricle, sacculus, and lagena), are filled with endolymph, a potassium-rich fluid that plays an essential role in the sensory signal transduction process. Each canal has an expansion known as an ‘ampulla’ containing a crista, cov ered by a gelatinous cupula, which is deformed by fluid movements during head/body motion. The canals detect turning movements of the head/body about their respective axis (Figure 2), thus acting as force transducers of angular acceleration. The utricle contains a single calcium carbo nate stone, called an ‘otolith’, overlying a fixed macula of hair cells and this organization is highly effective for trans ducing linear acceleration. The presence of single otolithic masses in teleosts is the reason for initially referring to these sensory structures as otolith organs (see also Hearing and Lateral Line: Auditory System Morphology). The major role of the utricle in fish relates to sensing inertia through detection of static changes in head/body position relative to the Earth’s gravitation vector, thereby creating an internal frame of reference for establishing egocentric direction responsible for orientation and locomotor behaviors. These major utricular roles observed in fish fit well with an earlier evolutionary appearance of this end organ than that of the semicircular canals, which require a critical spatial dimension to allow fluid movements for the detec tion of head motion. For this reason, it seems inappropriate to call the peripheral vestibular end organs simply the inner ear (see also Hearing and Lateral Line: Biomechanics of the Inner Ear in Fishes). Peripheral hair cells in both the lateral line/electro sensory neuromasts on the body surface as well as the specialized vestibular/auditory end organs in the inner ear are chemically linked to first-order afferent nerve
fibers that forward the sensory signals to distinct nuclear regions in the dorsal hindbrain. Vestibular afferent fibers that innervate the different semicircular canal organs and utricle are segregated from all other VIIIth nerve compo nents. In addition, vestibular afferents project exclusively to the most lateral octavolateral subgroups in the hind brain. Based on an evolutionarily conserved neuronal projection to brainstem and spinal regions, largely responsible for the control of balance and locomotion, the lateral portions of the octavolateral nuclei can be distinguished from the more medial and dorsal nuclei that process acoustic and lateral line sensory signals (Figure 3).
Central Location of Vestibular-Related Octavolateral Nuclei The vestibular nuclei occupy a considerable part of the dorso-lateral hindbrain between the Vth and Xth cranial nerves (Figure 3) (see also Hearing and Lateral Line: Auditory/Lateral Line CNS: Anatomy). Comparison of morphological features in several species of fish generally identifies five major subdivisions of second-order neurons in the vestibular nuclei. Moreover, distinct functional groups, identified according to their neuronal signals, are associated with a particular behavior (e.g., eye or body motion) and correlate reasonably well with the anatomical map. The similarity of structure and function of the major vestibular cell groups that control eye, fin, body, and tail motion across different fish species, therefore, allows vesti buloocular, vestibulospinal, vestibulocommissural, and vestibulocerebellar neurons to be identified as distinct populations. By and large, the current delineation of ves tibular subgroups is based on: (1) regionally restricted terminations of first-order afferent fibers from the different peripheral vestibular end organs; (2) anatomical tract tracing from efferent projection areas in the midbrain, hindbrain, and spinal cord; and (3) electrophysiological
Hearing and Lateral Line | Vestibular System Anatomy and Physiology (a)
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Figure 3 Spatial arrangement of goldfish octavolateral vestibular nuclei. Schematic sagittal (a) and coronal (b) diagrams depicting the location of brainstem nuclei. Arrow with dashed line in the sagittal view indicates the level of the coronal section. Abd, abducens motor nucleus; AO, DO, MO, PO, anterior, descending, medial, posterior octavolateral nuclei; CC, crus cerebelli; GT, gustatory tract; IIIn, VIIn, VIIIn, IXn, Xn, and Vn, oculomotor, facial, vestibular, glossopharyngeal, vagal, trigeminal nerves; MAN, medial auditory nucleus; MLF, medial longitudinal fasciculus; MED, medial nucleus; PLL, posterior lateral line nucleus; Ret, reticular formation; T, tangential nucleus.
correlates of second-order neurons during different beha vioral paradigms. The most comprehensive topographical mapping and electrophysiological studies have been car ried out in goldfish (Carassius auratus), and this species is used here as an example to summarize the overall organization of the vestibular subgroups within the octa volateral nuclei.
Origin of the Octavolateral Vestibular Subgroups All vestibular subgroups take their origin from a hindbrain segmental framework, which begins in early development as eight well-defined neuroepithelial compartments. The early embryonic hindbrain patterning serves as a mechan istic guide that directs the development of particular vestibular functional phenotypes involved in stabilization of retinal images and body posture. Combinatorial expres sion of spatially restricted regulatory genes plays a dominant patterning role in the development of any neu ron, vestibuloocular, or vestibulospinal, in any of the eight hindbrain compartments. This genetically specified com partmental blueprint is conserved between all species of fish, as well as for subsequent terrestrial vertebrates with only minor modifications. Vestibular neuronal subgroups evolved long before modern fishes in the earliest and now-extinct groups of jawless vertebrates. Interestingly, in living lampreys, the two vertically oriented semicircular canals, anterior and posterior (Figure 2), contribute equally to detection of the horizontal components of angular head acceleration. Hence, there are two well-delineated horizontal vestib ular subgroups in the hindbrain. However, a third (horizontal) canal was added to the ontogenetic blue print in modern sharks and fishes (Figure 2) such that
the two separate horizontal vestibular subgroups receive a common afferent input from one canal rather than a separate signal from the original anterior and posterior canal design. Notably, this structural design of two sepa rate horizontal vestibular subgroups, unique to central horizontal eye movement circuitry, has been conserved ever since it evolved in jawless fishes to present-day mammals. Ever since the earliest jawless vertebrates, the vesti bular subgroups appear to align with the peripheral location of the anterior and posterior semicircular canals surrounding a central otolith. However, such a stereo typed arrangement is more apparent than real because first-order vestibular afferents exhibit the capability to contact neurons in any of the vestibular subnuclei. Thus, it is likely that the vestibular system in jawless and jawed fishes was quickly converted from a point-to-point, hardwired canal/otolith projection to a highly integrated net work in which the appropriate vestibular signal could be utilized independent of the canal of origin but more dependent on the functional role of the targeted motor circuit. The primitive vestibular system largely relayed purely sensory signals to subsets of neurons that effectively could both generate and relay online signals to motor nuclei. However, in most cases, the vestibular signal can be equally correlated with the sensory stimulus (head motion) or the motor response (eye motion). It turns out that, quite early in evolution, fishes had converted the sensory-related neural activity in many of their vestibular subgroups into motor coordinates (e.g., as seen in goldfish second-order neurons) that exhibit all of the horizontal eye movement signals for visuo-vestibular-induced eye movements. From a systems control point of view, the vestibular subgroups are much more than simple sensory relay neurons; they also represent the motor command
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for appropriate contractions of eye, fin, body, and tail muscles.
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Central Terminations of Semicircular Canal and Utricular Afferents The distribution of first-order afferent fibers from indivi dual canals and the utricle allows individual vestibular nuclei to be recognized with respect to the direction of head/body motion. Anterior and posterior canal afferents terminate predominantly, though not exclusively, in the anterior octavolateral nucleus (AO) and the tangential nucleus (T) (Figure 3). Afferent projections from these two canals are less dense in the descending octavolateral nucleus (DO) and the posterior octavolateral nucleus (PO) (Figure 3). In contrast, the horizontal canal afferent termination coincides with one set of smaller neurons in the magnocellular octavolateral nucleus (MO), as well as more uniformly in another subset located throughout DO and T (Figure 3). First-order utricular afferents termi nate predominantly in MO, T, and DO, thus overlapping to a considerable extent with those from the horizontal canal. Significant for all sensorimotor behaviors in fish, there are virtually no vestibular nuclei that receive exclu sive afferent projections from a single peripheral end organ. Rather, first-order afferents overlap more or less completely, even though hot spots of terminations of fibers from particular vestibular organs exist in some nuclei. This widespread vestibular afferent pattern thus differs from topological maps of other sensory systems such as the closely related visual system. The absence of a sensory point-to-point map is consistent with the finding that signal processing in central vestibular nuclei is spa tially organized more according to efferent (largely motor) targets rather than topological hindbrain location. Observations on the distribution of afferent inputs are, in turn, quite compatible with the demonstrated roles of the vestibular subgroups in sensorimotor transformations contributing to the control of gaze (eye/head) and posture.
Hindbrain Vestibuloocular Origins and Projections to Extraocular Motor Nuclei Perhaps the dominant structural attribute of the vesti bular system is the spatially precise projection of vestibular subgroups to extraocular motoneurons located in the oculomotor, trochlear, and abducens nuclei. These three-neuronal VOR pathways consisting of first- and second-order vestibular and extraocular motoneurons are responsible for compensatory, 3D eye movements in all species of fish. Continuous, unblurred
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PC Figure 4 Extraocular muscles and pulling directions (view from dorsal) are illustrated with respect to semicircular canal orientation. Horizontal (HC, red), anterior (AC, green), and posterior vertical canal (PC, blue) are aligned with matching pairs of synergistic ipsi- and contralateral eye muscles (see matching color codes). LR, MR, lateral, medial rectus; IO, SO, inferior, superior rectus; IR, SR, inferior, superior rectus.
vision during high frequency and large amplitudes of head motion would not be possible without the vestibu lar nuclei. Compensatory eye movements are produced in fish, as in all other vertebrates, by a set of six eye muscles that insert on each eye bulb, such that any horizontal, verti cal, or torsional movement can be performed (Figure 4). A major organizational principle of the angular VOR is the approximate alignment of the axes of a particular semicircular canal and the pulling directions of syner gistic sets of two extraocular muscles (Figure 4). This arrangement illustrates the intricate link that has evolved between sensory and extraocular reference frames that in many species nearly perfectly stabilizes vision in response to eye/head body motion. The ves tibular neuronal subgroups critical for sensorimotor transformation of angular as well as linear acceleration signals are located laterally within the borders of AO and DO/PO (Figure 3). In general terms, the fundamental rule underlying any vestibuloocular connection is matching the spatial vector orientations for body movements around the roll and pitch axes with the extraocular motoneurons producing vertical and tor sional eye movements. Afferent input from the two vertical canals comprises the major input for vestibular subgroups activating extraocular muscles (SR, IR, SO, and IO) with corresponding spatially aligned pulling directions (Figure 4). Second-order vestibular neurons form behaviorally different and spatially nonoverlapping subgroups
Hearing and Lateral Line | Vestibular System Anatomy and Physiology
within the vestibular portion of the octavolateral nuclei. The functionally distinguishable oculomotor/ trochlear-projecting vestibuloocular neurons originate mainly from a rostral (AO) and to a minor extent from a caudal vestibular area (DO/PO). Each respective subgroup of vestibuloocular neurons receives afferent labyrinthine input from either the anterior or posterior vertical semicircular canal compatible with the spatial specificity of their target vertical and oblique extraocular motoneurons (SO, IO, SR, and IR). An additional organizational principle of the vestibulomo tor projections is a push–pull arrangement that allows excitation of particular sets of eye muscles and simul taneous inhibition of the respective sets of antagonists. Accordingly, vestibuloocular projections consist of inhibitory neurons, whose axons remain ipsilateral, and excitatory neurons, whose axons cross the midline
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to match agonist/antagonistic extraocular motor tar gets. Axons from the excitatory and inhibitory vestibuloocular subgroups reach their respective sub divisions in the oculomotor/trochlear nuclei by pathways in the ipsi- or contralateral medial longitu dinal fasciculus (MLF) (Figure 3).
Horizontal Vestibuloocular Subgroups Horizontal eye movements (upper panel in Figure 5) are particularly important for scanning the visual horizon and both eyes move conjointly producing conjugate movements that together encompass a much larger oculomotor range. However, conjugacy of eye movements in fish is much more apparent than real because a fovea is absent and the fusion of targets between the two eyes (stereoscopic vision) is
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Figure 5 Brainstem circuitry and compensatory conjugate horizontal angular vestibuloocular reflexes. Both right (blue) and left (red) eye motion are equal and opposite to horizontal head rotation as illustrated best by the eye vs. head velocity traces. A simplified view of the brainstem vestibuloocular pathways is shown in the lower schematic.
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limited, if present at all. The classical push–pull organiza tion present for vertical eye movements with a nearly mirror-symmetrical, crossed excitation, and an uncrossed inhibition is only established for abducens motoneurons that innervate the ipsilateral lateral rectus (LR) muscle and internuclear neurons that innervate the contralateral medial rectus (MR; Figure 5). There is no direct uncrossed vestibular inhibition of MR motoneurons because internuc lear neurons receive the same vestibular inhibitory input as LR motoneurons. This intrinsic difference in organization likely facilitates an independent bilateral activation of MR motoneurons for converging eye movements without activation of the LR motoneurons and vice versa for con vergence and divergence eye movements. The principal vestibular subgroups implicated in the horizontal VOR conveying a dynamic head/eye velocity signal are located in the ventral part of DO with projections to four separate, ventrally located, subgroups of abducens (Abd) motoneurons and internuclear (AI) neurons (simpli fied view with single subgroups in Figure 5). A subgroup of horizontal head velocity neurons is located in the rostral MO that project exclusively to ipsilateral MR motoneur ons. While the head velocity signal on AI and MO subpopulations might be considered as redundant, it likely is not, because the MO neurons subserve an essential highfrequency vestibular role not provided by AI neurons. In addition, this vestibular subgroup is maintained in mam mals, giving rise to a well-delineated pathway (ascending tract of Deiter’s) to the oculomotor nucleus. The highly conserved locations of horizontal canal-related, secondorder vestibuloocular neurons within the vertebrate hind brain clearly indicate an organizational principle centered on motor coordinates rather than topography of spatially segregated inputs from the sensory periphery. Both vertical and horizontal canal-related vestibulo ocular neurons are complemented by a densely clustered subgroup that forms the T nucleus just caudal to the VIIIth nerve entry (Figure 3). The functional role of this nucleus is clearly demonstrated by the close relationship between torsional angle of the eye and head tilt that appears even in larval fish before semicircular canals become operational. This nucleus serves as a gravito inertial center with crossed excitatory projections to the midbrain oculomotor/trochlear nuclei and the contra lateral spinal cord. Second-order vestibular neurons in the tangential nucleus receive major inputs from the utricle as well as minor inputs from the three canals in a spatially specific pattern. In contrast to vestibular neu rons in the semicircular canal-specific nuclei, tangential neurons exhibit a sustained sensitivity after small tonic changes of the head position, clearly indicating an appreciable tonic utricular influence. The likely conver gence of spatially specific afferent canal inputs with sensory signals from utricular sectors with the same spatial vector orientation in individual tangential
neurons forms a structural substrate that makes this nucleus a gravitoinertial relay center for vestibuloocular as well as postural reflexes.
Vestibulospinal Projections for Locomotor Control and Posture Stabilization Vestibulospinal projections control gravitoinertial-related postural reflexes through the activation of spinal inter neurons and motoneurons. Vestibular signals to spinal targets exhibit either low dynamics that are more corre lated with changes in body posture, or high dynamics that are involved in the initiation of fast locomotor actions. Vestibulospinal neurons are generally well localized within a restricted region that coincides with a central position along the rostro-caudal extent of the vestibular areas in the octavolateral nuclei. This central location within the vestibular column is compatible with an early evolutionary appearance of gravitoinertial function utiliz ing utricular signals for compensating pitch and roll deviations of body position in space. The populations of ipsi- and contralaterally descending vestibulospinal neu rons largely located in MO and the dorsal part of DO are morphologically heterogeneous and convey otolith as well as semicircular canal signals to the spinal cord. A number of vestibulospinal neurons are also located in the T nucleus intermingled with those that project to the contralateral oculomotor/trochlear nuclei, suggesting that this nucleus serves as a gravitoinertial relay center coupling eye motion and body posture control.
Auxiliary Vestibular Connections for Gaze and Posture Control Commissural projections through midline crossing axons interconnect bilateral vestibular nuclei. Functionally, the spatially specific inhibitory brainstem commissural pro jections that interconnect vestibular neurons with bilateral coplanar canal-related signals (e.g., ipsilateral posterior–contralateral anterior; see Figure 4) reinforce the differential detection of angular head acceleration signals due to the mirror-image arrangement of the semi circular canals in the periphery on both sides. This connection increases the sensitivity for detection of angu lar head acceleration, such that very small signals can be distinguished. A somewhat similar organization exists for utricular commissural connections that link second-order vestibular neurons with signals from spatially aligned bilateral utricular epithelial sectors. However, the specific functional interconnections are more complex given the 360� response sensitivity of the sensory epithelium on each side. Vestibular commissural neurons that
Hearing and Lateral Line | Vestibular System Anatomy and Physiology
interconnect the two sides essentially subdivide into ros tral and caudal subgroups in the AO and DO/PO, respectively. Given the dense projection and termination of anterior and posterior semicircular canal afferent fibers in AO, DO, and PO regions where commissural neurons are located, these latter cell groups likely establish a push–pull connectivity to increase the sensitivity for detection of vertical coplanar semicircular canal signals. Vestibular projections to the vestibulolateral lobe of the cerebellum in fish play an important role in the adaptation and plasticity of gaze-stabilizing reflexes. These connections are evolutionarily very old and are based on an intimate phylogenetic linkage between the octavolateral nuclei and cerebellum. Both, first- and second-order vestibular projections, convey angular head/body acceleration as mossy fiber input to the gran ular layer of the vestibulocerebellum. In turn, Purkinje cells from the caudal lobe of the vestibulocerebellum provide a direct output to particular vestibuloocular sub groups. The major locations for vestibulocerebellar projection neurons are a rostral subgroup with ipsilateral projection predominance in AO and a second one in DO/PO. The caudal vestibular subpopulation is contig uous with another population of cerebellar-projecting neurons located ventrolaterally in the caudal hindbrain. Together, along with cerebellar-projecting inferior oli vary neurons, these populations appear to have a common ontogenetic origin, such that all precerebellar nuclei responsible for eye/head motion derive from a common caudal hindbrain region.
Conservation of Fish Vestibular Organization in Other Vertebrates Comparison of the spatial distribution of individual vestib ular end-organ terminations among different groups of fish, such as damselfish, goby, toadfish, and elasmobranchs, reveals a vestibular pattern similar to that in goldfish. Notably, central projections from comparable populations of vestibular neurons originate from corresponding sub divisions, even though specific morphological details, particularly size, differ between the various species. This conservation also includes connectivity with particular targets, even in the exceptional case of flatfish, where both peripheral and central structural rearrangements occur during development. A comparison of vestibular system anatomy and physiology of fish with tetrapods also reveals a remarkably conserved pattern. In fact, affer ent projections from the different vestibular end organs in all tetrapod taxa terminate differentially in areas that cor respond to those in fish. Moreover, similar subgroups of major vestibular projection neurons originate from homo logous positions in the hindbrain of mammals, birds,
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and amphibians. These comparative attributes suggest that, from basic wiring through function, the vestibular blueprint was established quite early during vertebrate evolution and has been largely conserved unchanged throughout 400 million years of vertebrate phylogeny. See also: Detection and Generation of Electric Signals: Detection and Generation of Electric Signals in Fishes: An Introduction. Hearing and Lateral Line: Auditory/Lateral Line CNS: Anatomy; Auditory System Morphology; Lateral Line Neuroethology; Lateral Line Structure; Psychoacoustics: What Fish Hear; The Ear and Hearing in Sharks, Skates, and Rays.
Further Reading Gibbs MA and Northcutt RG (2004) Development of the lateral line system in the shovelnose sturgeon. Brain Behavior and Evolution 64: 70–84. Graf W and Baker R (1983) Adaptive changes of the vestibulo-ocular reflex in flatfish are achieved by reorganization of central nervous pathways. Science 221: 777–779. Graf W and Baker R (1985) The vestibuloocular reflex of the adult flatfish. II. Vestibulooculomotor connectivity. Journal of Neurophysiology 54: 900–916. Graf W, Spencer R, Baker H, and Baker R (1997) Excitatory and inhibitory vestibular pathways to the extraocular motor nuclei in goldfish. Journal of Neurophysiology 77: 2765–2779. Highstein SM, Kitch R, Carey J, and Baker R (1992) Anatomical organization of the brainstem octavolateralis area of the oyster toadfish, Opsanus tau. Journal of Comparative Neurology 319: 501–518. Maruska KP and Tricas TC (2009) Central projections of octavolateralis nerves in the brain of a soniferous damselfish (Abudefduf abdominalis). Journal of Comparative Neurology 512: 628–650. McCormick CA and Braford MR, Jr. (1994) Organization of inner ear endorgan projections in the goldfish, Carassius auratus. Brain Behavior and Evolution 43: 189–205. McCormick CA and Hernandez DV (1996) Connections of octaval and lateral line nuclei of the medulla in the goldfish, including the cytoarchitecture of the secondary octaval population in goldfish and catfish. Brain Behavior and Evolution 47: 113–137. McElligott JG, Beeton P, and Polk J (1998) Effect of cerebellar inactivation by lidocaine microdialysis on the vestibuloocular reflex in goldfish. Journal of Neurophysiology 79: 1286–1294. Pastor AM, De la Cruz RR, and Baker R (1994) Eye position and eye velocity integrators reside in separate brainstem nuclei. Proceedings of National Academy of Sciences of the United States of America 91: 807–811. Pastor AM, De la Cruz RR, and Baker R (1997) Characterization of Purkinje cells in the goldfish cerebellum during eye movement and adaptive modification of the vestibulo-ocular reflex. Progress in Brain Research 114: 359–381. Pastor AM, Torres B, Delgado-Garcia JM, and Baker R (1991) Discharge characteristics of medial rectus and abducens motoneurons in the goldfish. Journal of Neurophysiology 66: 2125–2140. Straka H and Dieringer N (2004) Basic organization principles of the VOR: Lessons from frogs. Progress in Neurobiology 73: 259–309. Suwa H, Gilland E, and Baker R (1996) Segmental organization of vestibular and reticular projections to spinal and oculomotor nuclei in the zebrafish and goldfish. Biological Bulletin 191: 257–259. Suwa H, Gilland E, and Baker R (1999) Otolith ocular reflex function of the tangential nucleus in teleost fish. Annals of the New York Academy of Sciences 871: 1–14. Tomchik SM and Lu Z (2005) Octavolateral projections and organization in the medulla of a teleost fish, the sleeper goby (Dormitator latifrons). Journal of Comparative Neurology 481: 96–117.