Unmasking of Spiral Ganglion Neuron Firing Dynamics by Membrane Potential and Neurotrophin-3

Abstract

Type I spiral ganglion neurons have a unique role relative to other sensory afferents because, as a single population, they must convey the richness, complexity, and precision of auditory information as they shape signals transmitted to the brain. To understand better the sophistication of spiral ganglion response properties, we compared somatic whole-cell current-clamp recordings from basal and apical neurons obtained during the first 2 postnatal weeks from CBA/CaJ mice. We found that during this developmental time period neuron response properties changed from uniformly excitable to differentially plastic. Low-frequency, apical and high-frequency basal neurons at postnatal day 1 (P1)-P3 were predominantly slowly accommodating (SA), firing at low thresholds with little alteration in accommodation response mode induced by changes in resting membrane potential (RMP) or added neurotrophin-3 (NT-3). In contrast, P10 -P14 apical and basal neurons were predominately rapidly accommodating (RA), had higher firing thresholds, and responded to elevation of RMP and added NT-3 by transitioning to the SA category without affecting the instantaneous firing rate. Therefore, older neurons appeared to be uniformly less excitable under baseline conditions yet displayed a previously unrecognized capacity to change response modes dynamically within a remarkably stable accommodation framework. Because the soma is interposed in the signal conduction pathway, these specializations can potentially lead to shaping and filtering of the transmitted signal. These results suggest that spiral ganglion neurons possess electrophysiological mechanisms that enable them to adapt their response properties to the characteristics of incoming stimuli and thus have the capacity to encode a wide spectrum of auditory information.

Neuronal heterogeneity and stereotyped connectivity in the auditory afferent system

“…Activation of K v channels shapes the pattern of neuronal firing and excitability and drives the rate of adaptation to sustained stimuli 23 . Their differential expression could participate in the expected distinct physiological characteristics of the different subclasses of type I neurons 5 , 8 , 24 (Fig. 3d–f and Supplementary Fig.…”

Heterogeneous intrinsic excitability of murine spiral ganglion neurons is determined by Kv1 and HCN channels

“…For example, altered neuronal membrane potential abolished rebound burst firing in thalamocortical neurons (Kim and McCormick, 1998). In spiral ganglion neurons, the regulation of holding potential on neuronal output was also observed in a subset of rapidly accommodating neurons that could be transformed into slowly accommodating neurons with a change of holding potential (from -80 to -60 mV, Crozier and Davis, 2013). …”

“…The endogenous properties of spiral ganglion neurons in explant cultures undergo dramatic changes in intrinsic excitability during the first 2 weeks prior to hearing onset (Crozier and Davis, 2013). The majority of changes in excitability stabilize by postnatal day 4 (P4) such that spiral ganglion neurons from P14 animals retain both regional as well as tonotopic characteristics of voltage thresholds presented herein (Crozier and Davis, 2013).…”

“…The majority of changes in excitability stabilize by postnatal day 4 (P4) such that spiral ganglion neurons from P14 animals retain both regional as well as tonotopic characteristics of voltage thresholds presented herein (Crozier and Davis, 2013). In addition, evidence from our laboratory indicates that K v 1 channel distribution, among other important regulators of spiral ganglion neuron function such as the tonotopic gradient of neurotrophin-3, AMPA receptor distribution, and other potassium channels, are expressed with similar tonotopic trends in adult animals as postnatal animals when assessed with immunocytochemistry (Adamson et al, 2002b, Flores-Otero and Davis, 2011).…”

Early Postnatal NT‐3 Gene Delivery Enhances Hearing Acquisition in the Developmental Period

“…Several studies have shown that exogenous NTs enhanced survival and neurite extension in vitro . Kondo et al demonstrated that SGN survival and neurite number were more strongly enhanced by NT3 than by BDNF at E18 culture, and Jin et al showed that combinations of NTs (NT3 + BDNF + leukemia inhibitory factor) could increase SGN survival better than single or other combinations, and these NTs were known to modulate neuronal activity through ion channel regulations …”