Gradients in the biophysical properties of neonatal auditory neurons align with synaptic contact position and the intensity coding map of inner hair cells

Abstract

<jats:p>Sound intensity is encoded by auditory neuron subgroups that differ in thresholds and spontaneous rates. Whether variations in neuronal biophysics contributes to this functional diversity is unknown. Because intensity thresholds correlate with synaptic position on sensory hair cells, we combined patch clamping with fiber labeling in semi-intact cochlear preparations in neonatal rats from both sexes. The biophysical properties of auditory neurons vary in a striking spatial gradient with synaptic position. Neurons with high thresholds to injected currents contact hair cells at synaptic positions where neurons with high thresholds to sound-intensity are found in vivo. Alignment between in vitro and in vivo thresholds suggests that biophysical variability contributes to intensity coding. Biophysical gradients were evident at all ages examined, indicating that cell diversity emerges in early post-natal development and persists even after continued maturation. This stability enabled a remarkably successful model for predicting synaptic position based solely on biophysical properties.</jats:p>

Functional subgroups of cochlear inner hair cell ribbon synapses differently modulate their EPSC properties in response to stimulation

“…Thus the differences between synapses are likely more subtle than this general analysis can identify or perhaps the differences in SGN properties are more associated with postsynaptic excitation properties. Recent data from both frog and mammal suggests that postsynaptic fibers vary in fundamental properties like input resistance, membrane potential and spike threshold; additional ( 21 , 34 ) investigations are needed to evaluate excitability based on synapse location.…”

“…Postsynaptic specializations need further quantification to demonstrate the key properties of EPSCs needed to generate sustained spiking ( 34 ) (see Ref. 21 , #530).…”

“…Postsynaptically, pillar-side boutons have bigger glutamate receptor patches compared with the modiolar side ( 20 ). Recent data suggest that high thresholds to injected current correspond with high threshold sound detection ( 21 ). Thus both, pre- and postsynaptic mechanisms likely contribute to establishing the SR and dynamic range of SGNs.…”

Similarities in the Biophysical Properties of Spiral-Ganglion and Vestibular-Ganglion Neurons in Neonatal Rats

“…Liu and Davis (2007) proposed the idea intrinsic diversity in voltage thresholds contributes to functional diversity I the auditory nerve (i.e., diversity in sound-intensity threshold and spontaneous rates across auditory neurons). Recent work in spiral ganglion shows that the biophysical diversity and transcriptomic diversity of ganglion neurons aligns (Petitpré et al, 2018;Shrestha et al, 2018;Sun et al, 2018;Markowitz and Kalluri, 2020) with a previously described spatial map for spontaneous rates and sound-intensity thresholds (Liberman, 1982). The somata of auditory nerve fibers contacting the pillar face of inner hair cells (putative high-spontaneous rate fibers) have lower current thresholds, higher-input impedance, and longer first-spike latencies compared to the somata of fibers contacting the modiolar face of the inner hair cell (putative low-spontaneous rate fibers) (Markowitz and Kalluri, 2020).…”

“…Recent work in spiral ganglion shows that the biophysical diversity and transcriptomic diversity of ganglion neurons aligns (Petitpré et al, 2018;Shrestha et al, 2018;Sun et al, 2018;Markowitz and Kalluri, 2020) with a previously described spatial map for spontaneous rates and sound-intensity thresholds (Liberman, 1982). The somata of auditory nerve fibers contacting the pillar face of inner hair cells (putative high-spontaneous rate fibers) have lower current thresholds, higher-input impedance, and longer first-spike latencies compared to the somata of fibers contacting the modiolar face of the inner hair cell (putative low-spontaneous rate fibers) (Markowitz and Kalluri, 2020). Differences in temporal integration could contribute to the response of SR-groups by making neurons selective to the different kinetics of synaptic current.…”