A Study of Postsynaptic Nicotinic Receptors in the Inner Ear

Oyinlolu Adeyanju¹, Dwayne D. Simmons²
Biology Department, Washington University, St. Louis, MO¹, Department of Auditory Neurophysiology, Washington University School of Medicine, Central Institute for the Deaf²

Sound affects nearly every aspect of our daily living, and in a world of alarms, crowds, music, and conversation, we need to be able to handle sounds appropriately. The inner ear is the primary site for the initial processing and digestion of the sounds we hear in our environment and is also where our brain manages and filters what sounds are transmitted. Our inner ears use nicotinic acetylcholine receptors (nAChRs) to mediate the synaptic transmission between the olivocochlear (OC) axons coming from the brain and the hair cells in inner ear. Very little is known about postsynaptic nicotinic receptors outside of the neuromuscular junction.

While we are aware of the efferent OC innervation of sensory hair cells in the adult, the manner in which they form nicotinic synapses remains a mystery. Right now, the focus of our research is geared towards what happens in the earliest stages of development of nicotinic synapses in the inner ear.

The interaction between efferent axon terminals and hair cells is mostly unknown. In fact, a major question concerning our work is whether efferent terminals or hair cells determine how and when these efferent synapses form. Using prenatal and newborn rats and mice, our studies have shown that the OC axons arrive much earlier than previously expected. Our data also suggest that efferent terminals appear before we can detect he presence of nAChRs in hair cells, raising the possibility that efferent OC axons may initiate nicotinic synapse formation.

For our experiments, we isolate inner ear organs at different stages of development and then apply fluorescent labels in order to visualize hair cells, OC terminals and nAChRs. Bungarotoxin (BTX), a snake venom toxin, is used to label postsynaptic nAChRs on hair cells. BTX, tagged with a fluorescent molecule, binds to the nicotinic receptors and is visualized using a laser scanning confocal microscope. After labeling hair cells and efferent OC terminals, confocal images of these BTX-labeled organs are collected and analyzed.

This study should lead to a better understanding of hearing and the way the neurons connect together during development.