Axodendritic versus axosomatic cochlear efferent termination is determined by afferent type in a hierarchical logic of circuit formation

Hearing involves a stereotyped neural network communicating cochlea and brain. How this sensorineural circuit assembles is largely unknown. The cochlea houses two types of mechanosensory hair cells differing in function (sound transmission versus amplification) and location (inner versus outer compartments). Inner (IHCs) and outer hair cells (OHCs) are each innervated by a distinct pair of afferent and efferent neurons: IHCs are contacted by type I afferents receiving axodendritic efferent contacts; OHCs are contacted by type II afferents and axosomatically terminating efferents. Using an Insm1 mouse mutant with IHCs in the position of OHCs, we discover a hierarchical sequence of instructions in which first IHCs attract, and OHCs repel, type I afferents; second, type II afferents innervate hair cells not contacted by type I afferents; and last, afferent fiber type determines if and how efferents innervate, whether axodendritically on the afferent, axosomatically on the hair cell, or not at all.