RESEARCH

Growing evidence from recent studies by our group and others suggests that factors intrinsic to the spiral ganglion neurons (SGNs) are key regulators for establishing and maintaining appropriate synapses with their target hair cells during development.

Spiral Ganglion Neurons

Type I and Type II

The cochlea contains two types of SGNs, type I and type II, which innervate the inner (IHC) and outer (OHC) hair cells, respectively. These two types of neurons are structurally and functionally different.

 

Type I SGNs make up the majority of the SGNs, approximately 90-95%, and are the main cells to transmit complex sound information to the brain.

 

The remaining 5 to 10% of SGNs are type II neurons that make synapses with the OHCs, which act as sound amplifiers.

Type I0%
Type II0%

Maturation and maintenance of the SGNs and their synaptic connections with the hair cells involves coordinated processes of axonal growth, synapse formation, and pruning of excess synapses formed during development. These processes, important for establishing functional cochlear neural circuits, differ between type I and type II and among the different subtypes of type I SGNs. Yet, genes and pathways regulating synaptic maturations and maintenance are largely unknown.

We are in a unique position to identify the genes that drive these processes because our lab has generated a transgenic mouse that allows us to sort SGNs into pure populations of type I and type II neurons.

Exploration of the genetic differences between type I and type II SGNs

To define the networks of genes that promote SGNs type I and type II-specific aspects of functional maturation, we have recently performed a comparison of SGNs using fluorescence-activated cell sorting followed (FACS) followed by a whole transcriptome microarray analysis.

This study contributes to the identification of several transcription factors, signaling molecules, and ion channels that are encoded by type I and type II-differentially expressed genes.

Exploration of the genetic differences between subtypes of type I SGNs

During development, each SGNs type I adopts specific morphological, molecular, and electrophysiological proprieties to enable them to interpret and transmit complex sounds stimuli. Recent studies suggest that different subtypes of type I SGNs differ in their vulnerability to age and/or noise induced degeneration or auditory neuropathy.

While this local heterogeneity is an important feature of the type I SGNs, it is still unclear whether it is determined by endogenous or exogenous factors. Our research aims to identity and investigate genes that define and maintain the functional heterogeneity of these different subtypes using single cell transcriptome analysis.

Approaches

mouse audiometry icon

Mouse Genetics and Audiometry

electrophysiology icon

Electrophysiology

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Microscopy

cell and molecular biology icon

Cell and Molecular Biology

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Bioinformatics

SCHEMATIC REPRESENTATION OF EXPERIMENTAL APPROACHES

By Stacy Levichev