Johns Hopkins University, Department of Neuroscience
 

 

 

 

Paul  Fuchs, Ph.D

John E. Bordley Professor of Otolaryngology- Head and Neck Surgery

Telephone Number:   (410) 955-6311

Fax Number:   (410) 614-4748

Johns Hopkins University

School of Medicine

Department of Otolaryngology, Head and Neck Surgery

Baltimore, MD 21205

Room: 818 Ross Bldg.

pfuchs1@jhmi.edu

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. Three main topics are studied here.

     1. Identification, function and developmental regulation of hair cell ion channels. Cochlear hair cells only gradually acquire mature function during development.  Hair cells can generate receptor potentials, and transmit afferent neurons, prior to the onset of hearing (about postnatal day 12 in rats and mice).  Indeed, this ‘spontaneous’ activity of the cochlea is thought to guide synapse formation in the central nervous system, and may contribute to activity-dependent maturation of the hair cells.  With the onset of hearing, various features of transmission change, as does the complement of ion channels expressed by hair cells. 

     2. Afferent synaptic function of cochlear hair cells. Hair cells, like photoreceptors and bipolar cells of the retina, release neurotransmitter at specialized structures called 'ribbon synapses'.  We have examined this process by intracellular recording from afferent synaptic boutons at their point of contact with the synaptic ribbon. The high resolution of these recordings has revealed unexpected details, suggesting that the ribbon is designed to enable the release of multiple vesicles simultaneously. The mechanisms of release, and the effect on afferent excitability, continue to be studied in the laboratory of Dr. Elisabeth Glowatzki, another member of research division of Otolaryngology.  In collaboration with Dr. David Yue of the Department of Biomedical Engineering, we have turned our attention to the hair cell’s voltage-gated calcium channels.  Calcium channel gating is subject to modulation by a number of calmodulin-like proteins.  These may combine to establish the set-point for tonic transmitter release from hair cells, which in turn appears to be important for enabling the rapid and precise timing of transmitter release. 

     3. 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.


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