Abstract
In the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation. The effects of peripheral firing patterns on spontaneous activity in the central auditory system are not well understood. Here, we describe wide-spread bilateral coupling of spontaneous activity that coincides with the period of transient efferent modulation of inner hair cells from the brainstem medial olivocochlear system. Knocking out α9/α10 nicotinic acetylcholine receptors, a requisite part of the efferent pathway, profoundly reduces bilateral correlations. Pharmacological and chemogenetic experiments confirm that the efferent system is necessary for normal bilateral coupling. Moreover, auditory sensitivity at hearing onset is reduced in the absence of pre-hearing efferent modulation. Together, these results demonstrate how afferent and efferent pathways collectively shape spontaneous activity patterns and reveal the important role of efferents in coordinating bilateral spontaneous activity and the emergence of functional responses during the prehearing period.
Highlights
In the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation
We observed that inter-peak intervals (IPI) decreased monotonically from P0 to P12 (Supplementary Fig. 1d), consistent with the monotonic increase of event frequency (Fig. 1e)
Previous studies showed that the presence of efferent cholinergic synapses, expression of relevant molecular machinery, and inner hair cells (IHC) responsiveness to acetylcholine all follow a similar temporal profile to the developmental timeline of bilateral correlations we describe here[14,15]
Summary
In the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation. Patterns of spontaneous firing of IHCs change across development and vary by tonotopic position in the immature cochlea[11,12], feeding variable ascending inputs to central circuits. During this time period, IHCs’ activity is modulated by transient efferent feedback from medialolivocochlear (MOC) neurons[13,14,15,16], which depends on α9/α10 nAChRs and coupled short-conductance potassium (SK2) channels[17]. Our results indicate a profound influence of the MOC system, a descending efferent circuit, in coordinating ascending tonotopic bilateral spontaneous activity throughout the auditory system and promoting normal auditory circuit development
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