Johns Hopkins School of Medicine

Excitability and Synaptic Function of Cochlear Hair Cells

We use a combination of biophysical, molecular genetic and histological techniques to examine excitability and synaptic function in mechanosensory hair cells of the vertebrate cochlea. These sensory cells transduce mechanical inputs into receptor potentials whose waveform and amplitude encode the information content of sound. A specific complement of voltage and ligand-gated ion channels shape the receptor potential for each hair cell and determine the timing and efficacy of transmitter release. Presently we focus on two main topics.

1. The cholinergic inhibition of hair cells. Efferent neurons from the brainstem inhibit cochlear hair cells by the release of acetylcholine. We have identified two of the ion channels involved in the cholinergic response, an unusual nicotinic receptor, and a small conductance, calcium-activated potassium channel.  We collaborate with Dr. A.B. Elgoyhen of the University of Buenos Aires (who first cloned the hair cell’s acetylcholine receptor subunits) to study transgenic mouse models in which specific alterations have been made in these proteins.  An unresolved question concerns the role of intracellular calcium stores in augmenting cholinergic inhibition.  Our work on efferent synapses has recently expanded to include mechanisms of plasticity that modify the efficacy of inhibitory feedback. 

2.  Type II cochlear afferents.  These unmyelinated neurons make up a small minority of the afferent innervation of the cochlea, and till recently little was known of their function.  We’ve used patch-clamp recording in excised cochlear tissue to study these mysterious neurons.  Emerging evidence suggests that type II afferents would be activated only by damaging levels of sound.  Thus they may function analogously to C fibers that subserve pain and temperature sensation in the somatic nervous system.  If proven true this provides new insights into pathogenic mechanisms of peripheral disorders such as hyperacusis and tinnitus.   

Public Lectures

NPR Lecture - All Things Considered - Science Friday - "Hearing Loss Pill"

Carnegie Lecture - "How the Ear Hears, and Sometimes Doesn’t"

National Public Radio – “Talk of the Nation/Science Friday”

“Hearing Loss Pill” 01/23/09 - “Ear-splitting Sounds” 10/23/09

Carnegie Institute Washington, DC: Capital Science Evenings

Institute for Basic Biomedical Sciences at Hopkins - "About Us," - "The Beauty and Biology of the Inner Ear" - "Now Hear This" - "Surviving Dance Club Music (Noise) With Hearing Intact"