The organization and function of medial rectus and inferior rectus non-twitch motoneurons in the oculomotor nucleus of monkey

The extraocular muscles in mammals, the effector organs of the oculomotor system, are fundamentally different from skeletal muscle. All extraocular muscles consist of two different layers, an orbital and a global layer. There are two basic categories of the muscle fibers: twitch or singly-innervated muscle fiber (SIF) and non-twitch or multiply-innervated muscle fiber (MIF). Previous studies in monkey revealed that SIF and MIF motoneurons are anatomically separated and have different premotor inputs. SIF and MIF motoneurons were identified by tracer injection into the belly, or the distal myotendinous junction, of the eye muscles. There are two groups of MIF motoneurons in the oculomotor nucleus, the C- and S-group. The C-group motoneurons innervate the medial rectus (MR) and inferior rectus (IR), while S-group motoneurons innervate the superior rectus and inferior oblique muscles. The motoneurons of C-group are located around the periphery of the oculomotor nucleus. We investigated the location of MR and IR MIF motoneurons in C-group, and the dendritic spread of MR compared with IR MIF motoneurons. We found that the MR and IR MIF motoneurons are two different populations of neurons in C-group. They lie relatively separated. The MR MIF motoneurons are located more dorsomedially than IR MIF motoneurons. The pattern of dendritic spread of these two MIF motoneurons is also different. The dendrites of IR MIF motoneurons spread into the supraoculomotor area bilaterally, but do not approach the Edinger-Westphal nucleus, in contrast, the dendrites of MR MIF motoneurons extend into the supraoculomotor area and the Edinger-Westphal nucleus unilaterally. The function of Edinger-Westphal nucleus is associated with the “near response”. In conclusion, the different location and different dendritic trees suggest that MR and IR MIF motoneurons have different functions. The IR MIF motoneurons may help to stabilize the eye position along with MIF motoneurons from other eye muscles, while the MR MIF motoneurons might also participate the vergence eye movements

Electrophysiological profile and monosynaptic circuitry of efferent vestibular nucleus neurons

As with other sensory modalities, the vestibular system recruits efferent circuitry to transport information from the central nervous system (CNS) to the sensory periphery. This efferent vestibular system (EVS) originates in the brainstem and terminates on vestibular hair cells and afferent fibres in the semicircular canals and otolith organs. Understanding how this central component outputs to the vestibular organs, and mediates motor and vestibular coordination, could potentially impact clinical treatment of vestibular disorders. Previous EVS work has primarily focused on the anatomy, pharmacology, synaptic mechanisms, and peripheral effects of efferent vestibular nucleus (EVN) activation. Although this work is fundamental to understanding this system and its mechanism of action, the behavioural function of the EVS is yet to be ascribed. For this, we need to appreciate the physiology of EVN neurons, and their context of activation within the CNS. In this thesis, I characterise the electrophysiological profile of EVN neurons, and trace their direct monosynaptic circuitry. My methodology includes whole-cell current- and voltage- clamp electrophysiology, and glycoproteindeficient rabies virus tracing techniques. Using these, I enrich understanding of EVN action, and hint at potential functional roles from their CNS partners. The data presented in this thesis provides novel insights into the EVS. EVN neurons are characterised with a homogeneous output, but a heterogeneous synaptic input profile. Inputs to the EVN originate from diverse areas in the brainstem and cortex. These findings suggest that the EVN modulates vestibular end organs in multiple different behavioural contexts. This work forms the basis of subsequent EVS behavioural investigations such as loss of function experiments targeting input regions via optogentic means and subsequent EVS recordings, or silencing of EVN activity and subsequent behavioural testing. Collectively, my results, these future directions, and the existing body of EVS literature, brings us closer than ever to understanding and ascribing a functional role for the EVS

Connections of the vestibular nuclei in the rabbit

This thesis descnbes the afferent, efferent and intrinsic connections of the vestibular nuclei in the Dutch belted rabbit. Different anatomical tracing techniques were used to study these projections. A description of the vestibular complex was added, since recent data for the rabbit are scarce (Chapter 2). A comparison between cytoarchitecture and staining for acetylcholinesterase and cytochromoxidase supported the subdivision of the central magnocellular area of the vestibular complex into a dorsal region comprising the lateral vestibular nucleus of Deiters and the ventrally located magnocellular portion of the medial vestibular nucleus. Additional evidence supporting this distinction came from a detailed analysis of the primary vestibular input in the rabbit (Chapter 3). The central projections of the vestibular nerve were investigated with anterograde axonal transport of wheatgerm agglutinin conjugated horseradish peroxidase (WGA-HRP) and tritiated leucine following injection in the vestibular ganglion. Labeled fibers and terminal ramifications were observed throughout the vestibular complex, including the magnocellular part of the medial vestibular nucleus, but they were absent from lateral vestibular nucleus. The absence of a projection of the vesnbular nerve to lateral vestibular nucleus is in accordance with the findings in other mammals (Voogd, 1964, Korte, 1979, Carleton and Carpenter, 1984). Termination in the cortex was restricted to the vermis. Small numbers of mossy fiber terminals were present bilaterally, close to the midline in lobules I and II, and in the depth of the main fissures separating the lobules II- VI. In the posterior vermis labeled mossy fiber terminals were found in lobule X and the ventral aspect of lobule IXd. Here the entire ipsilateral hemivermis contained many terminals, while contralaterally fewer mossy fiber tenninals were present in the medial one-third of these lobules. Labeled mossy fibers and terminals were absent from the flocculus and adjacent ventral paraflocculus

Assessment of Utricular Nerve, Hair Cell and Mechanical Function, in vivo.

Vestibular research currently relies on single response measures such as ex vivo hair cell and in vivo single unit recordings. Although these methods allow detailed insight into the response properties of individual vestibular hair cells and neurons, they do not provide a holistic understanding of peripheral vestibular functioning and its relationship to vestibular pathology in a living system. For this to take place, in vivo recordings of peripheral vestibular nerve, hair cell and mechanical function are needed. The previous inability to record vestibular hair cell responses stemmed from a difficulty in accessing the vestibular end-organs and stimulating them in isolation of the cochlea. To circumvent this, we developed a ventral surgical approach, removing the cochlea, to provide full access to the basal surface of the utricular macula. This allowed functional and mechanical utricular hair cell recordings, alongside gross utricular nerve responses. Recordings were performed in anaesthetized guinea pigs using Bone Conducted Vibration (BCV) and Air Conducted Sound (ACS) stimuli, providing a clinical link to vestibular reflex testing. We have thus far performed experiments involving: 1) Selective manipulation of vestibular nerve function, using electrical stimulation of the central vestibular system. 2) Glass micropipette recordings from the basal surface of the macular epithelium, which provided a robust and localized measure of extracellular utricular hair cell function. 3) With the macular exposed, we have measured the dynamic motion of the macula using Laser Doppler Vibrometry, which was recorded alongside the hair cell and nerve response recordings. 4) We have used physiological and pharmacological experimental manipulations to selectively modulate utricular nerve, hair cell or mechanical function, demonstrating the ability to differentially diagnose the basis of peripheral vestibular disorders in the mammalian utricle. These tools allow for a more complete understanding of peripheral vestibular function and a first order perspective into clinical disorders effecting the otoliths

Dynamic displacement of normal and detached semicircular canal cupula

© 2009 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in JARO - Journal of the Association for Research in Otolaryngology 10 (2009): 497-509, doi:10.1007/s10162-009-0174-y.The dynamic displacement of the semicircular canal cupula and modulation of afferent nerve discharge were measured simultaneously in response to physiological stimuli in vivo. The adaptation time constant(s) of normal cupulae in response to step stimuli averaged 36 s, corresponding to a mechanical lower corner frequency for sinusoidal stimuli of 0.0044 Hz. For stimuli equivalent to 40–200 deg/s of angular head velocity, the displacement gain of the central region of the cupula averaged 53 nm per deg/s. Afferents adapted more rapidly than the cupula, demonstrating the presence of a relaxation process that contributes significantly to the neural representation of angular head motions by the discharge patterns of canal afferent neurons. We also investigated changes in time constants of the cupula and afferents following detachment of the cupula at its apex—mechanical detachment that occurs in response to excessive transcupular endolymph pressure. Detached cupulae exhibited sharply reduced adaptation time constants (300 ms–3 s, n = 3) and can be explained by endolymph flowing rapidly over the apex of the cupula. Partially detached cupulae reattached and normal afferent discharge patterns were recovered 5–7 h following detachment. This regeneration process may have relevance to the recovery of semicircular canal function following head trauma.Financial support was provided by the NIDCD R01 DC06685 (Rabbitt) and NASA GSRP 56000135 & NSF IGERT DGE- 9987616 (Breneman)

Fifth Symposium on the Role of the Vestibular Organs in Space Exploration

Vestibular problems of manned space flight are investigated for weightlessness and reduced gravity conditions with emphasis on space station development. Intensive morphological studies on the vestibular system and its central nervous system connections are included