Gaze stabilization during head motion is a complex behavioral response that is highly dependent upon a functioning vestibular system. In fact, vestibular insult often results in balance and gaze disorders. Remarkably, birds demonstrate profound spontaneous vestibular receptor regeneration following damage. However, recent findings have demonstrated that the vestibular mediated eye and head component responses that comprise gaze differ significantly following regeneration as compared to pre-lesion conditions. These findings suggest that the vestibular neural mechanisms underlying gaze control in response to motion have been modified during regeneration. In an effort to understand how vestibular functions recover following damage, the proposed project will examine the physiology of primary vestibular afferents and central nuclei neurons that sub-serve gaze. Experiments are designed to expand upon our extensive knowledge of the regarding the morphological regenerative development of vestibular receptors. For example, it is known that a tri-staged temporal sequence of receptor afferent regeneration occurs, in which bouton fibers recover first, followed by dimorph, then calyx afferents late. When complete, much of the topographic organization of regenerated afferents reproduced that of the normal morphogenetic phenotype. However, the regenerated innervation patterns differed significantly from normal fibers having less complex innervation structures. The question is then raised as to how these morphologic differences affect neural processing of motion information.
In Specific Aim 1, neurophysiological recordings of vestibular afferent responses to motion will be obtained during the three unique stages of receptor regeneration. In these studies, we will examine the spatial and temporal properties of afferent responses during their re-development. In addition, we will examine spatial discrimination thresholds to fine differences in motion direction.
Specific Aim 2 will examine the central vestibular neurons that specifically control the eye and head components of gaze behavior. Neurophysiological recordings will be performed on identified neurons that project either to the spinal cord or are eye movement related during the three stages of regeneration. Based upon previous behavioral gaze studies, we expect that vestibulospinal neurons will regain their response to motion early in order to stabilize the head. Later, eye movement related neurons will regain their response to motion.
Specific Aim 3 will address a related issue of the contribution of two classes of afferents based upon their discharge regularity. Previous studies have suggested that regular firing afferents are primarily involved in control of eye movements while irregular firing afferents are more involved in head stabilization. By utilizing a reversible method of galvanic silencing of irregular firing afferents, the relative contributions of regular and irregular fibers toward gaze will be examined.
Although the vestibuloocular reflex (VOR) is one of the most well understood neural systems in the brain, much less is known regarding the complimentary function of VOR, vestibulocollic reflex (VCR), and cervicocollic reflex (CCR) responses to adequately control gaze behavior. In addition our knowledge regarding the functional recovery of the neural substrates underlying the gaze compensation following vestibular receptor damage remains lacking. The current project seeks to Increase our fundamental understanding of the afferent, central vestibular neuron, and gaze behavior response recovery process, which is essential, before more effective treatments of vestibular system disorders can be realized.
|Zakir, M; Wu, L-Q; Dickman, J D (2012) Morphology and innervation of the vestibular lagena in pigeons. Neuroscience 209:97-107|
|McArthur, K L; Zakir, M; Haque, A et al. (2011) Spatial and temporal characteristics of vestibular convergence. Neuroscience 192:361-71|
|McArthur, Kimberly L; Dickman, J David (2011) Behavioral state modulates the activity of brainstem sensorimotor neurons. J Neurosci 31:16700-8|
|McArthur, Kimberly L; Dickman, J David (2011) State-dependent sensorimotor processing: gaze and posture stability during simulated flight in birds. J Neurophysiol 105:1689-700|