title: NMDA Receptors Enhance Spontaneous Activity and Promote Neuronal Survival in the Developing Cochlea.
abstract: Spontaneous bursts of activity in developing sensory pathways promote maturation of neurons, refinement of neuronal connections, and assembly of appropriate functional networks. In the developing auditory system, inner hair cells (IHCs) spontaneously fire Ca(2+) spikes, each of which is transformed into a mini-burst of action potentials in spiral ganglion neurons (SGNs). Here we show that NMDARs are expressed in SGN dendritic terminals and play a critical role during transmission of activity from IHCs to SGNs before hearing onset. NMDAR activation enhances glutamate-mediated Ca(2+) influx at dendritic terminals, promotes repetitive firing of individual SGNs in response to each synaptic event, and enhances coincident activity of neighboring SGNs that will eventually encode similar frequencies of sound. Loss of NMDAR signaling from SGNs reduced their survival both in vivo and in vitro, revealing that spontaneous activity in the prehearing cochlea promotes maturation of auditory circuitry through periodic activation of NMDARs in SGNs.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: YingXin
authors.initials: Y
authors.lastname: Zhang-Hooks
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Brain Science Laboratory, the Research Organization of Science and Technology, Ritsumeikan University, Shiga 525-8577, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mishina
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: dbergles@jhmi.edu.
authors.forename: Dwight E
authors.initials: DE
authors.lastname: Bergles
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000502:physiology*; D003051:Cochlea / Q000166:cytology / Q000254:growth & development*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013136:Spiral Ganglion / Q000166:cytology / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate