Abstract
The precise functional role of the Efferent Vestibular System (EVS) is still unclear, but the auditory olivocochlear efferent system has served as a reasonable model on the effects of a cholinergic and peptidergic input on inner ear organs. However, it is important to appreciate the similarities and differences in the structure of the two efferent systems, especially within the same animal model. Here, we examine the anatomy of the mouse EVS, from its central origin in the Efferent Vestibular Nucleus (EVN) of the brainstem, to its peripheral terminations in the vestibular organs, and we compare these findings to known mouse olivocochlear anatomy. Using transgenic mouse lines and two different tracing strategies, we examine central and peripheral anatomical patterning, as well as the anatomical pathway of EVS axons as they leave the mouse brainstem. We separately tag the left and right efferent vestibular nuclei (EVN) using Cre-dependent, adeno-associated virus (AAV)-mediated expression of fluorescent reporters to map their central trajectory and their peripheral terminal fields. We couple this with Fluro-Gold retrograde labeling to quantify the proportion of ipsi- and contralaterally projecting cholinergic efferent neurons. As in some other mammals, the mouse EVN comprises one group of neurons located dorsal to the facial genu, close to the vestibular nuclei complex (VNC). There is an average of just 53 EVN neurons with rich dendritic arborizations towards the VNC. The majority of EVN neurons, 55%, project to the contralateral eighth nerve, crossing the midline rostral to the EVN, and 32% project to the ipsilateral eighth nerve. The vestibular organs, therefore, receive bilateral EVN innervation, but without the distinctive zonal innervation patterns suggested in gerbil. Similar to gerbil, however, our data also suggest that individual EVN neurons do not project bilaterally in mice. Taken together, these data provide a detailed map of EVN neurons from the brainstem to the periphery and strong anatomical support for a dominant contralateral efferent innervation in mammals.
Highlights
Two separate and distinct efferent systems transmit information from the central nervous system to peripheral inner ear organs (Figure 1). (1) The olivocochlear (OC) system comprises medial and lateral olivocochlear neurons that innervate the cochlea; and (2) efferent vestibular system (EVS) consisting of efferent vestibular nucleus (EVN) neurons that innervate the vestibular organsMouse Efferent Vestibular System Anatomy (Ryugo et al, 2011; Cullen and Wei, 2021)
The two systems share similarities in form and function, and it has been tempting to consider them as operationally equivalent. Both auditory and vestibular efferent neurons are localized to the brainstem and they both have a similar mechanism of action, using cholinergic and peptidergic neurotransmitters to modify peripheral hair cell and primary afferent activity (Ryugo et al, 2011; Cullen and Wei, 2021)
To target the Efferent Vestibular Nucleus (EVN) we intracranially injected Cre-dependant associated virus (AAV) into Chat-Cre mice. This resulted in strong endogenous expression of eYFP and mCherry in the left and the right EVN, respectively (Figures 3A,B arrows), and could be clearly visualized using confocal microscopy without amplification with antibodies (Figure 3B)
Summary
Two separate and distinct efferent systems transmit information from the central nervous system to peripheral inner ear organs (Figure 1). (1) The olivocochlear (OC) system comprises medial and lateral olivocochlear neurons that innervate the cochlea; and (2) efferent vestibular system (EVS) consisting of efferent vestibular nucleus (EVN) neurons that innervate the vestibular organsMouse Efferent Vestibular System Anatomy (Ryugo et al, 2011; Cullen and Wei, 2021). The two systems share similarities in form and function, and it has been tempting to consider them as operationally equivalent Both auditory and vestibular efferent neurons are localized to the brainstem and they both have a similar mechanism of action, using cholinergic and peptidergic neurotransmitters to modify peripheral hair cell and primary afferent activity (Ryugo et al, 2011; Cullen and Wei, 2021). Both groups of efferent neurons are proportionately fewer in number when compared to their afferent counterparts, and both efferent systems branch extensively to provide a significant peripheral terminal distribution within their respective inner ear organs (Brown, 2011; Holt et al, 2011). Our study has attempted to fill in the anatomical gaps of the mouse EVS so that it would be possible to examine both the auditory and vestibular efferent systems in the same species
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