Pre- and postnatal development of efferent connections of the cochlear nucleus in the rat.

Although the connections of the auditory brainstem nuclei are well described in adult mammals, almost nothing is known concerning how and when these connections develop. The purpose of the present study was to describe the development of the efferent projections of the cochlear nucleus (CN), the first central relay station in the ascending auditory pathway of mammals. We used two tracers in rats aged between embryonic day 15 (E15) and postnatal day 14 (P14; birth in the rat is at E22 = P0). The carbocyanine dye DiI was applied into the CN in aldehyde-fixed tissue. The second tracer, biocytin, was applied into the ventral acoustic stria in an in vitro slice preparation. The ontogeny of the efferent projections from the CN could be divided into three periods. The first period (E15-E17) is characterized by axonal outgrowth. Axons traverse nuclei in the superior olivary complex and the lateral lemniscus and finally grow up into the inferior colliculus, but axon collaterals do not form during this period. The second period (E18-P5) is marked by pronounced collateral branching of CN fibers in auditory brainstem nuclei. Collateralisation in the contralateral inferior colliculus starts shortly before that in the ipsilateral superior olivary complex. The remaining auditory nuclei become successively innervated, as indicated by collaterals found in them. During the third period (P5-P14) terminal structures mature further, as shown by the morphological changes of the calyces of Held in the medial nucleus of the trapezoid body. In conclusion, our results show that the efferent connections from the cochlear nucleus form over a period of almost two weeks and are laid down without forming aberrant internuclear connections. On a nuclear level, an adult-like projection pattern is already achieved one week prior to the onset of physiological hearing.