Axogenesis in the human fetal auditory system, demonstrated by neurofilament immunohistochemistry

Morphological, electrophysiological and behavioral evidence indicates that the onset of rapid, synchronized conduction of auditory impulses occurs in the human brainstem during the 28th-29th fetal weeks. This implies that axonal connections in the brainstem auditory pathway are generated prior to this time. In order to investigate the sequence of axogenic events in the human brainstem pathway, we employed immunohistochemical techniques and an antibody to neurofilament protein. Immunostaining for axonal neurofilaments in an age-graded series of fetal brains demonstrates that a small number of cochlear nerve axons have invaded the ventral cochlear nucleus by the 16th fetal week. By this same time point, a limited number of trapezoid body-lateral lemniscus axons have reached the superior olivary complex and inferior colliculus. Between gestational weeks 16 and 26, there is marked expansion and collateralization of the ascending pathway from cochlear nerve to inferior colliculus. By week 26, ascending axons have begun to form plexuses of terminal neuropil within all of the brainstem auditory nuclei. Beginning in week 22, there is development of commissural axons (dorsal commissure of the lateral lemniscus and commissure of the inferior colliculus) and descending projections (descending collicular axons and olivocochlear bundle). This early establishment of a mature pattern of axonal connections presumably forms the basis for the appearance of myelin, acousticomotor reflexes and recordable brainstem responses by fetal week 29.