Three-dimensional visualization of the human membranous labyrinth: The membrana limitans and its role in vestibular form

The inner ear contains the end organs for balance (vestibular labyrinth) and hearing (cochlea). The vestibular labyrinth is comprised of the semicircular canals (detecting angular acceleration) and otolith organs (utricle and saccule, which detect linear acceleration and head tilt relative to gravity). Lying just inferior to the utricle is the membranous membrana limitans (ML). Acting as a keystone to vestibular geometry, the ML provides support for the utricular macula and acts as a structural boundary between the superior (pars superior) and inferior (pars inferior) portions of the vestibular labyrinth. Given its importance in vestibular form, understanding ML morphology is valuable in establishing the spatial organization of other vestibular structures, particularly the utricular macula. Knowledge of the 3D structure and variation of the ML, however, remain elusive. Our study addresses this knowledge gap by visualizing, in 3D, the ML and surrounding structures using micro-CT data. By doing so, we attempt to clarify: (a) the variation of ML shape; (b) the reliability of ML attachment sites; and (c) the spatial relationship of the ML to the stapes footplate using landmark-based Generalized Procrustes, Principal Component and covariance analyses. Results indicate a consistent configuration of three distinct bony ML attachments including an anterolateral, medial, and posterior attachment which all covary with bony structure. Our results set the stage for further understanding into vestibular and more specifically, utricular macula spatial configuration within the human head, offering the potential to aid in clinical and evolutionary studies which rely on a 3D understanding of vestibular spatial configuration.     

Alterations to vestibular morphology in highly bred domestic dogs may affect balance

The modern domestic dog (Canis lupus familiaris) provides an excellent model to examine the effects of cranial modification. Extreme variation in skull length among dog breeds due to high levels of selective breeding is known to be linked to disorders of the head and neck. Such alteration may also influence sensory organs including those of the vestibular system (VS), one of the most fundamental sense organs, essential in maintaining balance. Studies in mammals have shown that orientation of ipsilateral semicircular canals (SCCs) of the VS at right angles (orthogonality) is related to angular acceleration sensitivity. Due to their considerable variation in craniofacial form while exhibiting similar locomotion, domestic dogs provide an excellent natural experiment to examine if cranial alteration influences VS functional morphology. Our methods examine how change in cranial base length across dog breeds relates to SCC orthogonality using linear modeling and analyses of variance. The sample studied (29 bony labyrinths of 17 dog breeds) was obtained from a previous study on canid inner ear metrics. Results support the hypothesis that orthogonality between the anterior and posterior SCC + ampulla significantly correlates with cranial base length. This suggests a close relationship between the orientations of SCCs with their ampullae and cranial structure among dog breeds. Specifically, highly derived breeds, such as the brachycephalic pug, have anterior and posterior SCCs and ampullae that deviate the most from orthogonality. Therefore, such highly bred domestic dogs may also have altered vestibular function due to compressed cranial form.     

Development and evolution of the vestibular apparatuses of the inner ear

The vertebrate inner ear is a labyrinthine sensory organ responsible for perceiving sound and body motion. While a great deal of research has been invested in understanding the auditory system, a growing body of work has begun to delineate the complex developmental program behind the apparatuses of the inner ear involved with vestibular function. These animal studies have helped identify genes involved in inner ear development and model syndromes known to include vestibular dysfunction, paving the way for generating treatments for people suffering from these disorders. This review will provide an overview of known inner ear anatomy and function and summarize the exciting discoveries behind inner ear development and the evolution of its vestibular apparatuses.     

A phenomenon in vestibular compensation

The role of spinal afferentation from the lower half of the body in compensation of the sequelae of unilateral loss of vestibular function was studied in experiments on guinea pigs. Division of the spinal cord at the thoracic level under local anesthesia had no appreciable effect on the development of compensation after simultaneous or subsequent destruction of the labyrinth and did not disturb compensation in previously labyrinthectomized animals. Division of the spinal cord in labyrinthectomized animals under ether or chloroform anesthesia was accompanied by a sharp disturbance of compensation. These substances evoked a similar picture of decompensation in unilaterally labyrinthectomized animals with an intact spinal cord also. The results indicate that the disturbance of vestibular compensation discribed in the literature after division of the spinal cord under ether anesthesia is not the result of removal of spinal afferentation from the lower half of the body, but is due to the direct effect of inhalational anesthetics on compensation mechanisms.(Presented by Academician of the Academy of Medical Sciences of the USSR O. G. Gazenko.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 21–23, July, 1979.     

Activity of forelimb muscles under vestibular stimulation in guinea pigs with cerebellum removed

Using decerebrate guinea pigs, we investigated the effect of complete removal of the cerebellum upon the influence of the vestibular system over the modulation of locomotor activity. It was found that the influence of the vestibular system over locomotor activity is preserved after removal of the cerebellum. The dynamic characteristics of the vestibular-spinal influences in cerebellectomized animals differ insignificantly from those of animals with an intact cerebellum. It is concluded that preservation of cerebellar-vestibular connections is not a necessary condition for the realization of vestibular influences upon locomotor activity.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 75, No. 9, pp. 1230–1237, September, 1989.     

Acid-sensing ionic-channel functional expression in the vestibular endorgans

In the vestibular system, the electrical discharge of the afferent neurons has been found to be highly sensitive to external pH changes, and acid-sensing ionic-channels (ASIC) have been found to be functionally expressed in afferent neurons. No previous attempt to assay the ASIC function in vestibular afferent neurons has been done. In our work we studied the electrical discharge of the afferent neuron of the isolated inner ear of the axolotl (Ambystoma tigrinum) to determine the participation of proton-gated currents in the postransductional information processing in the vestibular system. Microperfusion of FMRF-amide significantly increased the resting activity of the afferent neurons of the semicircular canal indicating that ASIC currents are tonically active in the resting condition. The use of ASIC antagonists, amiloride and acetylsalicylic acid (ASA), significantly reduced the vestibular-nerve discharge, corroborating the idea that the afferent neurons of the vestibular system express ASICs that are sensitive to amiloride, ASA, and to FMRF-amide. The sensitivity of the vestibular afferent-resting discharge to the microperfusion of ASIC acting agents indicates the participation of these currents in the establishment of the afferent-resting discharge.     

M.I.T./Canadian vestibular experiments on the Spacelab-1 mission: 2. Visual vestibular tilt interaction in weightlessness

Summary Adaptation to weightlessness includes the substitution of other sensory signals for the no longer appropriate graviceptor information concerning static spatial orientation. Visual-vestibular interaction producing roll circularvection was studied in weightlessness to assess the influence of otolith cues on spatial orientation. Preliminary results from four subjects tested on Spacelab-1 indicate that visual orientation effects were stronger in weightlessness than pre-flight. The rod and frame test of visual field dependence showed a weak post-flight increase in visual influence. Localized tactile cues applied to the feet in space reduced subjective vection strength.     

Identification of a critical period for motor development in neonatal rats.

Manipulation of the developing nervous system has provided valuable insights into nervous system function. One important concept to arise from this type of study has been the identification of specific "critical periods" for the development of various functions. A critical period has been most clearly shown for the visual system where monocular eye closure for a few weeks led to functionally significant changes in visually guided behaviors and the connectivity of the visual cortex. Critical periods have also been defined for other sensory systems. Although studies of the effect of manipulating sensory systems during development are sometimes difficult to interpret (e.g. Ref. 7), this difficulty is compounded in the case of the motor system. Problems arise because manipulations of the postnatal motor system are difficult to implement and usually require invasive procedures such as tenotomy, neurotomy, and nerve crush (for review, see Ref. 17). We have approached the problem of manipulating the motor environment by adapting a paradigm widely used to study the experimental effects of simulated weightlessness in adult rats: namely, tail suspension. This method has several advantages for manipulating the motor system: (i) because it is noninvasive, it is less discomforting than neurotomy, tenotomy or nerve crush; (ii) it does not immobilize the animals, they move about the cage and extend and flex their hindlimbs; and (iii) it specifically examines the importance of load-bearing on the development of antigravity muscles and their neuronal circuits.(ABSTRACT TRUNCATED AT 250 WORDS)     

Study of compensation after unilateral loss of vestibular function

The dynamics of compensation of the after-effects of unilateral destruction of the labyrinth was studied in rabbits. Destruction of the labyrinth was followed by nystagmus, an increase in the external respiration and heart rates, and EEG activation. The investigations revealed differences in the rate of extinction of these reactions with time. In the late stages after labyrinthectomy marked asymmetry of the nystagmic response of the eyes to angular accelerations of equal intensity but opposite direction was observed. Stimulation of the intact otolith apparatus was accompanied by the appearance of positional nystagmus. The results point to imperfection of the mechanisms of compensation after total unilateral loss of vestibular function.Institute for Medico-Biological Problems, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 2, pp. 152–155, February, 1978.     

Neurogenesis and astrogenesis contribution to recovery of vestibular functions in the adult cat following unilateral vestibular neurectomy: cellular and behavioral evidence

In physiological conditions, neurogenesis occurs in restricted regions of the adult mammalian brain, giving rise to integrated neurons into functional networks. In pathological or postlesional conditions neurogenesis and astrogenesis can also occur, as demonstrated in the deafferented vestibular nuclei after immediate unilateral vestibular neurectomy (UVN) in the adult cat. To determine whether the reactive cell proliferation and beyond neurogenesis and astrogenesis following UVN plays a functional role in the vestibular functions recovery, we examined the effects of an antimitotic drug: the cytosine-β-d arabinofuranoside (AraC), infused in the fourth ventricle after UVN. Plasticity mechanisms were evidenced at the immunohistochemical level with bromodeoxyuridine, GAD67 and glial fibrillary acidic protein (GFAP) stainings. Consequences of immediate or delayed AraC infusion on the behavioral recovery processes were evaluated with oculomotor and posturo-locomotor tests. We reported that after UVN, immediate AraC infusion blocked the cell proliferation and decreased the number of GFAP-immunoreactive cells and GABAergic neurons observed in the vestibular nuclei of neurectomized cats. At the behavioral level, after UVN and immediate AraC infusion the time course of posturo-locomotor function recovery was drastically delayed, and no alteration of the horizontal spontaneous nystagmus was observed. In contrast, an infusion of AraC beginning 3 weeks after UVN had no influence neither on the time course of the behavioral recovery, nor on the reactive cell proliferation and its differentiation. We conclude that the first 3 weeks after UVN represent a possible critical period in which important neuroplasticity mechanisms take place for promoting vestibular function recovery: reactive neurogenesis and astrogenesis might contribute highly to vestibular compensation in the adult cat.     

A critical period for auditory thalamocortical connectivity

Neural circuits are shaped by experience during periods of heightened brain plasticity in early postnatal life. Exposure to acoustic features produces age-dependent changes through largely unresolved cellular mechanisms and sites of origin. We isolated the refinement of auditory thalamocortical connectivity by in vivo recordings and day-by-day voltage-sensitive dye imaging in an acute brain slice preparation. Passive tone-rearing modified response strength and topography in mouse primary auditory cortex (A1) during a brief, 3-d window, but did not alter tonotopic maps in the thalamus. Gene-targeted deletion of a forebrain-specific cell-adhesion molecule (Icam5) accelerated plasticity in this critical period. Consistent with its normal role of slowing spinogenesis, loss of Icam5 induced precocious stubby spine maturation on pyramidal cell dendrites in neocortical layer 4 (L4), identifying a primary locus of change for the tonotopic plasticity. The evolving postnatal connectivity between thalamus and cortex in the days following hearing onset may therefore determine a critical period for auditory processing.     

Vestibular compensation: tonic spinal influence upon spontaneous descending vestibular nuclear activity.

Guinea-pigs were used to study plastic changes of the nervous system associated with spinal decompensation (postural asymmetry). This phenomenon is elicited by a lesion or blockade to the spinal cord of an animal that has compensated to a unilateral vestibular neurectomy. Spinal preparations of compensated animals were monitored for the return of spinal reflex activity and then given a postbrachial spinal transection or a lumbar plexus blockade with 2% xylocaine. No decompensation asymmetry was measureable in passive resistance to stretch or in ongoing forelimb extensor and neck electromyographic activity. In other experiments integrated multiunit activity of the vestibular nuclei of ‘intact’ and ‘compensated’ animals was measured to determine the effects of cool blocks performed at spinal T-7. For a given locus, the net multiunit activity of the vestibular nuclei either did not change, decreased or increased in response to the T-7 cold block. In the 31 loci studied that proved to be in the descending vestibular nuclei (14 loci in 5 ‘intact’, and 17 loci in 5 ‘compensated’ animals), the mean response (to the block at T-7) in the descending vestibular nuclei of ‘intact’ animals was a 0.3% increase in spontaneous activity, while in the ‘compensated’ animals there was a mean 27.7% decrease in activity. This difference is statistically highly significant.Three mechanisms are proposed to account for this result and it is concluded that compensatory changes confined to the spinal cord are unlilely to account for body postural decompensation. Vestibular compensation involves the establishment of a tonic facilitatory influence of the spinal cord upon the descending vestibular nucleus ipsilateral to a vestibular neurectomy.     

Three-dimensional analysis of inner ear development in human embryos

The development of the inner ear is difficult to understand morphologically, because it proceeds in a complicated manner. Chronological 3-D reconstructed models of the inner ear primordium in human embryos (Carnegie stage 16-22) were created from the histological serial sections in the Kyoto Collection of Human Embryos using 3-D-reconstruction software on a personal computer. The endolymphatic duct begins to extend at stage 18 and continues to extend. The formation of the anterior and posterior semicircular ducts begins at stage 17. The upper lateral region of the otic pouch starts to sink inward at stage 17 and then the epithelia of both sides face and fuse with each other. The fusion disappears and the mesenchyme appears in the primordium, which looks like a hole in the otic pouch at stage 18. The mesenchyme begins to enlarge in the otic pouch at late stage 18, and continues to enlarge until the formation of the loop of semicircular ducts at stage 19. The lateral semicircular duct is formed similarly at stages 18 and 19. In the mesenchyme of the lateral semicircular duct, we found apoptotic death near the epithelium of the otic pouch at late stage 19. The cochlear duct already begins to extend at stage 16. First it extends to the opposite direction of the future cochlear rotation at stage 16 and 17, and then turns to the future rotating direction at stage 18. The cochlear duct initiates rotation at late stage 19. The cochlear duct continues to rotate and forms approximately one winding at stage 22.