Connecting the Inner Ear to the Central Auditory System: Molecular Development and Characteristics of the Primary Auditory Neurons and Their Network

Abstract

Spiral ganglion neurons are critical for hearing as they transmit auditory information in the form of electrical signals from mechanosensory hair cells in the inner ear to the cochlear nuclei in the brainstem. Loss of these auditory neurons and/or hair cells is the leading cause of congenital and acquired neurosensory hearing loss affecting hundreds of millions of people worldwide. The most common therapeutic strategies for hearing loss either use hearing aids to increase hair cell stimulation or utilize cochlear implants as an electronic substitute for hair cells. These devices, as well as normal hearing, all require the presence of healthy functional spiral ganglion neurons. This volume details the essential role of the auditory spiral ganglion neurons, elucidates and characterizes their development and loss, their electrophysiological characteristics, their connectivity to their targets in the inner ear and the brain, and discusses the potential for their restoration. A comprehensive review about the spiral ganglion neurons is important for researchers not only in the inner ear field but also in development, neuroscience, biophysics as well as neural networks researchers. The first chapter by Dabdoub and Fritzsch provides an overview of this volume and the current research on auditory neurons, including a perspective on future directions of research. Chapter 2 by Goodrich describes the molecular and genetic factors responsible for the neurogenesis of the spiral ganglion neurons. Chapter 3 by Fritzsch et al. explains the role of neurotrophic factors in the maintenance of the spiral ganglion neurons. The electrophysiological properties as well as the tonotopic organization of the spiral ganglion neurons are detailed in Chap. 4 by Davis and Crozier. Chapter 5 by Moser and Rutherford and Chap. 6 by Muniak and Ryugo reveal the connectivity details of the auditory neurons with hair cells in the inner ear and the cochlear nucleus in the brainstem, respectively. Chapter 7 by Green et al. details gains in our cellular and molecular understanding of spiral ganglion neurons derived from various in vitro techniques invented during the last 100 years to achieve a mechanistic understanding for enhanced translation. Lang in Chap. 8 reviews processes of spiral ganglion neuron degeneration and dysfunction and their relationship to hearing loss. The final Chap. (9) by Nayagam and Edge introduces stem cell research to replace lost auditory neurons. This volume provides an up-to-date source of information on the spiral ganglion neurons. From neurogenesis to biophysics and stem cell replacement therapy, the comprehensive and wide-ranging subjects encompassed will ensure that this volume will enlighten and function as a catalyst for future research and discovery. While loss of auditory neurons has been considered secondary to hair cell loss, an increasing body of evidence clearly indicates that auditory neurons can degenerate as a direct result of noise exposure and aging while hair cells remain intact. Therefore, auditory neurons are a primary target for regeneration and a better understanding of these neurons will ultimately result in long-term maintenance and accelerate regenerative therapies.