Cochlear Neurotransmission Group
The Cochlear Neurotransmission Group studies the generation and propagation of neural signals in the inner ear. Our laboratories use biophysical, electrophysiological, molecular biological and histological methods to determine fundamental molecular mechanisms by which neurotransmitters are released from primary sensory cells (‘hair cells’) to excite second order neurons carrying information to the brain. We apply these same techniques to study inhibitory feedback produced by brain neurons that project to and regulate the sensitivity of the cochlea.
Our studies concentrate on the properties of voltage and/or ligand-gated ion channels and transporters expressed in hair cells, neurons and supporting cells of the cochlea. Ion channels, neurotransmitter receptors and transporters are therapeutic targets for the treatment of virtually all diseases of the nervous system.
Discoveries from this laboratory will help advance therapeutic approaches to hearing loss by identifying these essential molecules and defining their functional roles in the cochlea.
Paul A. Fuchs, Ph.D. Professor, Department of Otolaryngology-Head and Neck Surgery
Elisabeth Glowatzki, Ph.D. Associate Professor, Department of Otolaryngology–Head and Neck Surgery
In addition to sending information to the brain, the inner ear is subject to feedback regulation from the brain. Neurons in the superior olivary complex of the brainstem send axons out to the cochlea where they release the neurotransmitter acetylcholine to inhibit mechanosensory hair cells. By recording from individual hair cells during this inhibitory process, we have shown that their acetylcholine receptors are related to the nicotinic receptors found in skeletal muscle, but with quite unusual pharmacology.
Surprisingly, while acetylcholine excites skeletal muscle via its nicotinic receptors, hair cells are inhibited by theirs. Calcium ions play a central role in nicotinic inhibition, serving as a second messenger to activate potassium channels that hyperpolarize the hair cell. The molecular mechanisms underlying these native inhibitory processes may provide candidate approaches for therapeutic intervention.
- Glowatzki E and PA Fuchs (2000). Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea. Science 288:2366-2368.
- Juan Diego Goutman, Paul Albert Fuchs and Elisabeth Glowatzki (2005). Facilitating efferent inhibition of inner hair cells in the cochlea of the neonatal rat. Journal of Physiology 566: 49-59.
- Jee-Hyun Kong, John P. Adelman and Paul A. Fuchs. (2008). Expression of the SK2 calcium-activated potassium channel is required for cholinergic function in cochlear hair cells. Journal of Physiology 586:5471-85.
- Taranda J, Maison SF, Ballestero JA, Katz E, Savino J, Vetter DE, Boulter J, Liberman MC, Fuchs PA, Elgoyhen AB (2009). A point mutation in the hair cell nicotinic cholinergic receptor prolongs cochlear inhibition and enhances noise protection. PLoS Biol. 2009 Jan 20;7(1):e18.
Sounds in the world around us are converted into neuro-electrical signals in the inner ear, or cochlea. Mechanosensory ‘hair cells’ generate tiny voltage changes depending on the intensity and frequency composition of a sound wave.
That initial voltage signal is communicated to a second order neuron through the release of chemical neurotransmitters at specialized structures called dense bodies or ribbons (by analogy to similar connections in the retina). The mechanisms of neurotransmitter release and the ion channels that support it are studied by our laboratories.
- Glowatzki E and PA Fuchs (2002) Transmitter release at the hair cell ribbon synapse. Nature Neuroscience 5(2):147-154.
- Grant, L and PA Fuchs (2008). Calcium, calmodulin-dependent inactivation of calcium channels in inner hair cells of the rat cochlea. Journal of Neurophysiology 99(5):2183-93.
- Goutman J and E Glowatzki (2007) Time course and calcium dependence of transmitter release at a single ribbon synapse. Proc Natl Acad Sci U S A. 104(41):16341-6.
- Weisz C., E. Glowatzki and P.A. Fuchs (2009). The postsynaptic function of Type II cochlear afferents. Nature (in press).