The role of spontaneous activity in development of the endbulb of Held synapse.

In the mouse brainstem cochlear nucleus, the auditory nerve to bushy cell synapse (endbulb of Held) is specialised for rapid, high-fidelity transmission. Development of this synapse is modulated by auditory nerve activity. Here we investigate the role of spontaneous auditory nerve activity in synaptic transmission using deafness (dn/dn) mutant mice that have abnormal hair cells and lack spontaneous auditory nerve activity. Evoked and miniature alpha amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor-mediated excitatory post-synaptic currents (eEPSCs, mEPSCs) were compared in deafness and normal mice before the age of hearing onset (postnatal day 7-11: P7-11) using variance-mean, miniature event and tetanic depression analyses. Amplitudes were significantly greater in deafness mice for eEPSCs (2.1-fold), mEPSCs (1.4-fold) and quantal amplitudes (1.5-fold). eEPSCs in deafness mice decayed more rapidly with increasing age, indicating an input-independent transition in post-synaptic AMPA receptor properties. A comparison of normal mice before and after the onset of hearing showed a change in synaptic parameters with an increase in eEPSC (1.7-fold), mEPSC (1.6-fold) and quantal amplitude (1.7-fold) after hearing onset while release probability remained constant (0.5). Overall, the results in deafness mice suggest that synaptic strength is altered in the absence of spontaneous auditory nerve activity.