Current concepts in cochlear ribbon synapse formation

Abstract

In mammals, hair cells and spiral ganglion neurons (SGNs) in the cochlea together are sophisticated “sensorineural” structures that transduce auditory information from the outside world into the brain. Hair cells and SGNs are joined by glutamatergic ribbon-type synapses composed of a molecular machinery rivaling in complexity the mechanoelectric transduction components found at the apical side of the hair cell. The cochlear hair cell ribbon synapse has received much attention lately because of recent and important findings related to its damage (sometimes termed “synaptopathy”) as a result of noise overexposure. During development, ribbon synapses between type I SGNs and inner hair cells form in the time window between birth and hearing onset and is a process coordinated with type I SGN myelination, spontaneous activity, synaptic pruning, and innervation by efferents. In this review, we highlight new findings regarding the diversity of type I SGNs and inner hair cell synapses, and the molecular mechanisms of selective hair cell targeting. Also discussed are insights into cell adhesion molecules and protein constituents of the ribbon synapse, and how these factors participate in ribbon synapse formation. We also note interesting new insights into the morphological development of type II SGNs, and the potential for cochlear macrophages as important players in protecting SGNs. We also address recent studies demonstrating that the structural and physiological profiles of the type I SGNs do not reach full maturity until weeks after hearing onset, suggesting a protracted development that is likely modulated by activity.

Semaphorin-5B Controls Spiral Ganglion Neuron Branch Refinement during Development

“…As shown in Figures 1 and 2, Sema5B is expressed transiently in hair cells and is eliminated by P5. Given that SGN refinement events occur over an extended period (Huang et al, 2007;Liberman and Liberman, 2016;Coate et al, 2019), it is our expectation that the actions of Sema5B/PlexinA1 signaling represent only one component of this process. Other later events, such as thyroid hormone-mediated synaptic pruning signaling (Sendin et al, 2007;Sundaresan et al, 2016), likely also contribute to the entire refinement process.…”

“…At ϳE16.5, the type I SGNs retract from the OHC region to the IHC region (Coate et al, 2015;Druckenbrod and Goodrich, 2015) and the type II SGNs turn toward the base. Throughout this process, the type I SGNs shed their terminal branches as a prelude to establishing single, unramified bouton endings with IHCs (Coate et al, 2019). In the mature mouse cochlea, a single IHC will accommodate as many as 20 SGN synaptic endings (Meyer and Moser, 2010).…”

Insulin-Like Growth Factor 1 on the Maintenance of Ribbon Synapses in Mouse Cochlear Explant Cultures

“…IHCs contact type I SGNs and convey electrochemical signals to the central auditory system (Hudspeth, 1997 ). Synaptic connections between IHCs and type I SGNs have specialized synaptic constructions, termed ribbon synapses, and are important for auditory function (Safieddine et al, 2012 ; Coate et al, 2019 ).…”

Cnr2 is important for Ribbon Synapse Maturation and Function in Hair Cells and Photoreceptors

“…Notably, we found similar alterations in the inner ear. The importance of physiological activity for maturation of the ribbon synapse is well known and has gained a lot of attention in these last years (for review [89]) especially in regard to synaptopathies (discussed below). Our work clearly pointed to a cnr2mediated cross talk at the afferent synapse, thus offering a novel mechanistical link between maturation and activity.…”