Recovery of Gaze Stability During Vestibular Regeneration

Abstract

Haque A, Zakir M, Dickman JD. Recovery of gaze stability during vestibular regeneration. J Neurophysiol 99: 853-865, 2008. First published November 11, 2007 doi:10.1152/jn.01038.2007. Many motion related behaviors, such as gaze stabilization, balance, orientation, and navigation largely depend on a properly functioning vestibular system. After vestibular insult, many of these responses are compromised but can return during the regeneration of vestibular receptors and afferents as is known to occur in birds, reptiles, and amphibians. Here we characterize gaze stability in pigeons to rotational motion during regeneration after complete bilateral vestibular loss via an ototoxic antibiotic. Immediate postlesion effects included severe head oscillations, postural ataxia, and total lack of gaze control. We found that these abnormal behaviors gradually subsided, and gaze stability slowly returned to normal function according to a temporal sequence that lasted several months. We also found that the dynamic recovery of gaze function during regeneration was not homogeneous for all types of motion. Instead high-frequency motion stability was first achieved, followed much later by slow movement stability. In addition, we found that initial gaze stability was established using almost exclusive head-response components with little eye-movement contribution. However, that trend reversed as recovery progressed so that when gaze stability was complete, the eye component had increased and the head response had decreased to levels significantly different from that observed in normal birds. This was true even though the head-fixed VOR response recovered normally. Recovery of gaze stability coincided well with the three stage temporal sequence of morphologic regeneration previously described by our laboratory.

Regeneration of Vestibular Horizontal Semicircular Canal Afferents in Pigeons

“…As regeneration progressed (late stage 2), gaze stability returned for the mid-frequency rotations, followed lastly by recovery during slow rotational head movements. These later recovery dynamics coincided with the regeneration of calycealbearing afferents that innervated the central crista regions (Haque et al 2008). In mammals, the central regions of the cristae contain irregularly firing high-gain dimorph and lowgain calyx afferents with large dynamic ranges Fernandez et al 1988;Lysakowski et al 1995).…”

“…First, during stage 1 regeneration, exclusive formation of bouton afferents and hair cells exhibiting a type II morphologic phenotype were observed. Coincident to the afferent innervation development, we previously found that hair cells regenerated primarily in the peripheral regions of the canal cristae and otolith maculae, with fewer cells present in the central apex or striolar regions Haque et al 2008;Zakir et al 2006). Still, some afferents and hair cells did occupy these central regions and, when present, were always observed to exhibit a bouton innervation pattern.…”

“…Whether these differences in afferent innervation are related to the change in functional contribution between the head and eye components to gaze stability in regenerated birds is unknown. However, although pigeon gaze stability recovers to normal values, the relative contributions from the head and eye components change during regenerative recovery (Haque et al 2008). In fact, the eye component during head-free rotations increases, whereas the head component decreases in significance to total gaze stability, in converse to the behavior observed in normal birds (Haque and Dickman 2005;Haque et al 2008).…”

“…Still, head and eye responses partially recover (Stapely et al 2006), presumably using extravestibular motion cues to enhance central neural compensation (Newlands and Perachio 1990a,b;Zennou-Azogi et al 1994) and adaptation (Anastasio 1992;Serafin et al 1999) processes. Recently, we demonstrated that vestibular-mediated gaze stabilization during rotational motion recovers fully in birds undergoing regeneration, with a time course lasting several months (Haque et al 2008). Interestingly, gaze stability during high-frequency motion recovered first, at a time when only bouton afferents innervated the vestibular epithelia (stage 1 regeneration).…”

“…Remarkably, in many vertebrates, including amphibians, reptiles, and birds, spontaneous regeneration of hair cells and reinnervation of the receptor epithelium occurs (Corwin and Cotanche 1988;Masetto and Correia 1997a;Weisleder and Rubel 1992;Zakir and Dickman 2006). In addition, hair cell function (Masetto and Correia 1997b), afferent responses to motion (Boyle et al 2002;Li and Correia 1998), and vestibular-mediated behavioral responses (Carey et al 1996;Dickman and Lim 2004;Goode et al 1999;Haque et al 2008) have all been shown to recover during regeneration.…”