CHARACTERIZATION OF THE UNMYELINATED TYPE II AFFERENTSAS COCHLEAR NOCICEPTORS

[摘要] In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell.The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release, and are insensitive to sound.Their function has been mysterious for decades due to their scarcity and lack of specific genetic markers. Intriguingly, type II afferents remain intact in damaged regions of the cochlea while outer hair cells and type I afferents are damaged by noise exposure.In this thesis, using whole-cell patch clamp recordings directly from the dendrites of type II afferents, we found that the weak synaptic transmission is mediated by GluA2 containing AMPA receptors. In contrast, ATP released from the damaged cochlea more potently activates type II afferents. We show that type II afferents are strongly depolarized when outer hair cells are damaged.This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage.Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity that can accompany hearing loss.Exposure to the KCNQ channel activator retigabine suppressed the type II fiber’s response to hair cell damage.Type II afferents may be the cochlea’s nociceptors, prompting avoidance of further damage to the irreparable inner ear.

[发布机构] Johns Hopkins University

[效力级别] acoustic trauma

[关键词] ATP;acoustic trauma;hyperacusis;noxacusis;type II cochlear afferents;Neuroscience