Neural diversity can expand the encoding capacity of a circuitry. A striking example of diverse structure and function is presented by the afferent synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea. Presynaptic active zones at the pillar IHC side activate at lower IHC potentials than those of the modiolar side that have more presynaptic Ca2+ channels. The postsynaptic SGNs differ in their spontaneous firing rates, sound thresholds, and operating ranges. While a causal relationship between synaptic heterogeneity and neural response diversity seems likely, experimental evidence linking synaptic and SGN physiology has remained difficult to obtain. Here, we aimed at bridging this gap by ex vivo paired recordings of murine IHCs and postsynaptic SGN boutons with stimuli and conditions aimed to mimic those of in vivo SGN characterization. Synapses with high spontaneous rate of release (SR) were found predominantly on the pillar side of the IHC. These high SR synapses had larger and more temporally compact spontaneous EPSCs, lower voltage thresholds, tighter coupling of Ca2+ channels and vesicular release sites, shorter response latencies, and higher initial release rates. This study indicates that synaptic heterogeneity in IHCs directly contributes to the diversity of spontaneous and sound-evoked firing of SGNs.
Keywords: active zone; cochlear sound encoding; mouse; neuroscience; paired recordings; synaptic heterogeneity; synaptic vesicle.
From the rustling of falling leaves all the way to a roaring jet engine, our sense of hearing allows us to recognise a wide range of sounds that vary in pitch and intensity. Two groups of inner ear cells, known as the inner hair cells and the spiral ganglion neurons, perform this feat by encoding sounds into signals that can be processed by the nervous system. This mechanism relies on inner hair cells detecting sound vibrations and then causing spiral ganglion neurons to ‘fire’ electrical signals that can be relayed to the brain. Each inner hair cell connects to multiple spiral ganglion neurons through contact points called synapses, where information corresponding to specific sounds is transmitted. For any given pitch, different groups of spiral ganglion neurons encode different sound intensities (that is, loud versus soft sounds). Whether this is because these groups are fundamentally different in some way or because the synapses between neurons and hair cells have different properties remained to be elucidated. To investigate this question, Jaime Tobón and Moser examined the mechanisms underpinning sound encoding in the inner ear of mice, using tissue preparations containing inner hair cells and spiral ganglion neurons with fully intact synapses. Measuring the electrical properties on both the inner hair cell and spiral ganglion neuron side of individual synapses revealed differences in the levels of spontaneous activity of the synapses. Synapses with higher spontaneous activity detected softer stimuli, whereas those with lower rates responded only to stronger stimulation. Each type of synapse formed at different locations on the surface of inner hair cells, and they had different electrical properties that mirrored the firing diversity of the spiral ganglion neurons. In other words, it is the inner hair cell ‘side’ of the synapses that dictates the different responses of the neurons connected to them. To diversify the response of their synapses, the inner hair cells relied on variations in synaptic properties (such as voltage-dependent activation thresholds and the coupling of calcium channels and vesicular release sites) that determine how sensitive a cell is to an electric signal, and how quickly and efficiently it can react to it. These results shed new light on the biological mechanism of sound encoding, a process fundamental to our sense of hearing. In the future, Jaime Tobón and Moser hope that this knowledge may eventually inform the development of better aids and treatments for hearing loss patients.
© 2023, Jaime Tobón and Moser.