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Genetic Targeting and Conductance-Based Modeling Reveal Novel Diversity within Mouse Type II Spiral Ganglion Neurons
Nathaniel Nowak1,2, Radha Kalluri3,2,4,5
1Hearing and Communications Neuroscience Training Program, University of Southern California, Los Angeles, California 90057.
Abstract:
Spiral ganglion neurons (SGNs) transmit auditory signals from the cochlea to the brain and are divided into two main types: type I and type II, distinguished by their anatomy and connectivity. However, the function of type II SGNs remains poorly understood due to their scarcity and lack of clear physiological markers. In this study, we use two Cre-dependent fluorescent reporter mouse lines of both sexes to enhance the identification and targeting of type II SGNs for whole-cell patch-clamp recordings. We reveal a set of distinguishing biophysical features, notably, the presence of an inactivating potassium current and weaker voltage-gated sodium currents, which clearly separate type II SGNs from their type I counterparts. Additionally, we uncover greater-than-expected heterogeneity among type II SGNs, including variation in size, excitability, and ion channel expression. These features suggest distinct subtypes of type II SGNs, with potential differences in function. We find that most type II SGNs are relatively unexcitable and incapable of repetitive firing. Instead, they appear to be better suited to integrating sustained signals, potentially supporting roles in detecting cochlear damage or modulating efferent feedback. Additionally, through computational modeling, we demonstrate that removing the inactivation component of the inactivating potassium current specific to type II SGNs allowed repetitive spiking to similar levels seen in type I SGNs, suggesting the crucial role of the current in stifling type II SGN activity. Together, our findings define biophysical signatures that distinguish SGN types and subtypes, offering new insight into their contributions to normal hearing and cochlear pathology.

