NMDA Receptors Enhance Spontaneous Activity and Promote Neuronal Survival in the Developing Cochlea

• IHC-SGN synapses in the developing cochlea contain functional NMDARs
• NMDARs promote Ca2+ influx in SGN dendrites and increase repetitive firing
• NMDARs enhance coincident activation of neighboring SGNs during spontaneous events
• NMDAR signaling promotes survival of SGNs in vitro and in vivo

SummarySpontaneous 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 Ca2+ 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 Ca2+ 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.