Developmental spontaneous activity promotes sensory domains, frequency tuning and proper gain in central auditory circuits

Neurons that process sensory information exhibit bursts of electrical activity during development, providing early training to circuits that will later encode similar features of the external world. In the mammalian auditory system, this intrinsically generated activity emerges from the cochlea prior to hearing onset, but its role in maturation of auditory circuitry remains poorly understood. We show that selective disruption of cochlear supporting cell spontaneous activity suppressed patterned burst firing of central auditory neurons without impacting cell survival or acoustic thresholds. However, neurons within the inferior colliculus of these mice exhibited enhanced acoustic sensitivity and broader frequency tuning, resulting in wider isofrequency lamina. Despite this enhanced neural responsiveness, total tone-responsive regions of the midbrain and cortex were substantially smaller. Thus, loss of pre-hearing cochlear activity causes profound changes in neural encoding of sound, with important implications for restoration of hearing in individuals that experience disrupted activity during this critical developmental period.