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

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 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. Zhang-Hooks et al. find that NMDARs play a crucial role in development of the cochlea. By prolonging synaptic excitation at IHC-SGN synapses, NMDARs enhance repetitive firing of SGNs, increase dendritic Ca²⁺ influx, and promote SGN integration into the auditory pathway.