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Neuroscience. 2015 Jan 29;285:248-59. doi: 10.1016/j.neuroscience.2014.11.027. Epub 2014 Nov 25.

From development to disease: diverse functions of NMDA-type glutamate receptors in the lower auditory pathway.

Author information

1
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.
2
Weinberg College of Arts & Sciences, United States.

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.

KEYWORDS:

N-methyl-d-aspartate receptors; auditory development; auditory disease; glutamate; hearing

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