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School of Medicine
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Recent Findings on Efferent Synapses
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.