Talking back: Development of the olivocochlear efferent system

Abstract

Developing sensory systems must coordinate the growth of neural circuitry spanning from receptors in the peripheral nervous system (PNS) to multilayered networks within the central nervous system (CNS). This breadth presents particular challenges, as nascent processes must navigate across the CNS-PNS boundary and coalesce into a tightly intermingled wiring pattern, thereby enabling reliable integration from the PNS to the CNS and back. In the auditory system, feedforward spiral ganglion neurons (SGNs) from the periphery collect sound information via tonotopically organized connections in the cochlea and transmit this information to the brainstem for processing via the VIII cranial nerve. In turn, feedback olivocochlear neurons (OCNs) housed in the auditory brainstem send projections into the periphery, also through the VIII nerve. OCNs are motor neuron-like efferent cells that influence auditory processing within the cochlea and protect against noise damage in adult animals. These aligned feedforward and feedback systems develop in parallel, with SGN central axons reaching the developing auditory brainstem around the same time that the OCN axons extend out toward the developing inner ear. Recent findings have begun to unravel the genetic and molecular mechanisms that guide OCN development, from their origins in a generic pool of motor neuron precursors to their specialized roles as modulators of cochlear activity. One recurrent theme is the importance of efferent-afferent interactions, as afferent SGNs guide OCNs to their final locations within the sensory epithelium, and efferent OCNs shape the activity of the developing auditory system. This article is categorized under: Nervous System Development > Vertebrates: Regional Development.

Efferent feedback enforces bilateral coupling of spontaneous activity in the developing auditory system

“…Without the MOC-mediated mechanism that we identified, uncoupled streams of peripheral activity might decrease synchronous activity between presynaptic crossing fibers and postsynaptic auditory neurons, thus undermining bilateral circuit maturation. Moreover, the MOC-mediated bilateral coupling is itself tonotopic, consistent with the known efferent innervation pattern (Frank and Goodrich, 2018). Therefore, the MOC-mediated cochlea coupling can serve as a neural substrate that mimics the bilateral features of real-world stimuli and promotes Hebbian plasticity across two sides of the auditory system.…”

“…Our results revealed a changing profile of in vivo spontaneous activity and evolving bilateral connectivity in the auditory system that peaks early in the pre-hearing period and slowly declines prior to hearing onset. Intriguingly, the strength of bilateral coupling matched the time course of a transient cholinergic modulation imposed on inner hair cells by the medial-olivocochlear (MOC) efferent system (Katz et al, 2004, Elgoyhen and Katz, 2012, Kearney et al, 2019, Frank and Goodrich, 2018. Mice lacking the a9/a10 nicotinic acetylcholine receptor (nAChR), a necessary constituent of efferent modulation (Elgoyhen et al, 1994, Elgoyhen et al, 2001, Morley et al, 2017, displayed severly disrupted bilateral correlations.…”

Current concepts in cochlear ribbon synapse formation

“…And as a fifth event, the type I SGN peripheral processes become innervated by lateral olivocochlear (LOC) efferent axons (Bergeron, Schrader, Yang, Osman, & Simmons, ), which protect against sound‐evoked damage (Darrow et al, ) and may also regulate auditory input (Guinan, ). We note here that the SGNs must also compete for synaptic space on inner hair cells with medial olivocochlear (MOC) efferents, which make transient contacts with inner hair cells before innervating outer hair cells (Frank & Goodrich, ). Studies have shown efferent innervation starting as early as E18.5 in mouse cochleae (Bruce, Kingsley, Nichols, & Fritzsch, ) and soon after birth in rat cochleae (Knipper, Zimmermann, Rohbock, Köpschall, & Zenner, ; Simmons, ).…”

Expression of class III Semaphorins and their receptors in the developing chicken (Gallus gallus) inner ear

“…In both systems, the perception of sensory information depends upon mechanosensory transduction by hair cells (HCs) and the delivery of this information to the primary afferent neurons that make synaptic connections with the receptor cells (Lewis, Leverenz, & Bialek, ). Many research groups have investigated how classic axon guidance factors impact afferent innervation of the auditory and vestibular organs (Appler & Goodrich, ; Battisti, Fantetti, Moyers, & Fekete, ; Coate, Spita, Zhang, Isgrig, & Kelley, ; Defourny et al, ; Fekete & Campero, ; Frank & Goodrich, ; Ghimire, Ratzan, & Deans, ).…”

“…Many research groups have investigated how classic axon guidance factors impact afferent innervation of the auditory and vestibular organs (Appler & Goodrich, 2011;Battisti, Fantetti, Moyers, & Fekete, 2014;Coate, Spita, Zhang, Isgrig, & Kelley, 2015;Defourny et al, 2013;Fekete & Campero, 2007;Frank & Goodrich, 2018;Ghimire, Ratzan, & Deans, 2018).…”