Table of Contents

Genetic Targeting and Conductance-Based Modeling Reveal Novel Diversity within Mouse Type II Spiral Ganglion Neurons

  1. Radha Kalluri1,2,3,4
  1. 1Hearing and Communications Neuroscience Training Program, University of Southern California, Los Angeles, California 90057
  2. 2Caruso Department of Otolaryngology, Keck School of Medicine, University of Southern California, Los Angeles, California 90057
  3. 3Zilkha Neurogenetic Institute, Keck School of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90057
  4. 4Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, California 90057
  1. Correspondence should be addressed to Radha Kalluri at radha{at}usc.edu.
  1. Author contributions: N.N. and R.K. designed research; N.N. and R.K. performed research; R.K. contributed unpublished reagents/analytic tools; N.N. and R.K. analyzed data; N.N. and R.K. wrote the paper.

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.

Footnotes

  • This work was supported by NIH NIDCD Grants R01 DC015512 and T32 DC009975 and the Caruso Department of Otolaryngology at the University of Southern California. We thank Dr. Daniel Bronson, Katherine Regalado, and members of the Kalluri PIELab at USC, Department of Otolaryngology, and the Hearing and Communications Neuroscience Training Program for discussion. We thank Juan Llamas and Dr. Ksenia Gnedeva for teaching us the intracerebroventricular approach for injecting viral (AAV) vectors.

  • The authors declare no competing financial interests.

  • Received December 10, 2025.
  • Revision received June 29, 2026.
  • Accepted July 1, 2026.

Related Article

  1. The Journal of Neuroscience, 46(33): e2254252026

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