title: From development to disease: diverse functions of NMDA-type glutamate receptors in the lower auditory pathway.
abstract: N-methyl-D-aspartate receptors (NMDA-Rs) are located at each synapse in the lower auditory pathway of mammals and avians. Characterized by a slow and long-lasting excitatory response upon glutamate activation, their existence in a sensory system biologically engineered for speed and precision seems counterintuitive. In this review we consider the diverse functions of NMDA-Rs. Their developmental regulation and unique subunit composition in the inner ear promote protective and neurotrophic roles following acute insult by regulating AMPA-R expression and assisting in the restoration of synaptic inputs. This contrasts with chronic damage where overactivation of NMDA-Rs is implicated in neuronal death. These functions are thought to be involved in auditory diseases, including noise-induced hearing loss, neural presbycusis, and tinnitus via aberrant excitation. A more traditional role emerges in the developing auditory brainstem, where NMDA-Rs are downregulated and switch subunit composition with maturation. Their biophysical properties also contribute to synaptic dynamics resembling long-term plasticity. At mature synapses they support reliable auditory processing by increasing the probability of action potential generation, regulating first-spike latency, and maintaining reliable action potential firing. Thus, NMDA-R functions in the lower auditory pathway are diverse, contributing to synaptic development, plasticity, temporal processing, and diseases.
authors.affiliation: Roxelyn and Richard Pepper Department of Communication Sciences and Disorders, United States; The Hugh Knowles Hearing Research Center, United States; Northwestern University Interdepartmental Neuroscience Program, United States. Electronic address: jason.sanchez@northwestern.edu.
authors.forename: J T
authors.initials: JT
authors.lastname: Sanchez
authors.affiliation: Weinberg College of Arts & Sciences, United States.
authors.forename: S
authors.initials: S
authors.lastname: Ghelani
authors.affiliation: Weinberg College of Arts & Sciences, United States.
authors.forename: S
authors.initials: S
authors.lastname: Otto-Meyer
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000254:growth & development / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate
keywords: N-methyl-d-aspartate receptors; auditory development; auditory disease; glutamate; hearing