This is a project by Dr. Fuchs to study the biophysical mechanisms by which brainstem neurons exert inhibition of the sensory receptor cells of the cochlea. The sensitivity of the inner ear is controlled by central neurons whose axons project to the cochlea and there release the neurotransmitter, acetylcholine (ACh) to inhibit the cochlear cell (hair cells). While the actions of ACh are well-known on nerve and muscle, the hair cell cholinergic receptor and its physiological effect, are quite unusual. ACh inhibits hair cells first causing calcium entry, followed by a calcium-activated potassium current which actually hyperpolarizes, and inhibits, the cell. These actions are mediated by a neurotransmitter receptor that appears to be related to the nicotinic receptors of nerve and muscle. While unusual, there is some evidence that similar cholinergic effects may occur elsewhere in the brain. Dr. Fuchs will identify and study the mechanism of cholinergic inhibition of cochlear hair cells and its developmental regulation. He will use state-of-the-art techniques to explore these mechanisms and the hair cell ACh receptor will be characterized both pharmacologically and physiologically. This detailed study of the hair cell ACh receptor will provide fundamental insights into brain cholinergic systems.***//
