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The goals of the present study were to identify olivocochlear neurons in the human brainstem, to establish the time course of their early development and to compare the organization of the human olivocochlear system to that of other mammals. To accomplish these goals, we used immunohistochemistry for choline acetyltransferase (ChAT) and calcitonin gene-related peptide (CGRP) in postmortem brainstems of human subjects ranging in age from 16 fetal weeks to 17 years. By immunostaining, we identified two classes of cells in the superior olivary complex: both classes were seen to be present from the twenty-first fetal week to the seventeenth year. Neurons which are immunostained only for ChAT are located primarily in the dorsomedial, ventral and ventrolateral sectors of the periolivary region. These neurons are predominantly bipolar or multipolar cells, and are probably homologous to medial olivocochlear neurons in other species. A second population of cells is immunoreactive for both ChAT and CGRP. This population includes a cluster of mostly small oval neurons, located on the dorsal edge of the olivary complex, and a variable number of cells found along the margin of the lateral olivary nucleus. These ChAT- and CGRP-immunoreactive cells are likely to be homologous to the lateral olivocochlear system in other mammals. With increasing age, the dorsal cluster of small cells shifts from its original cap-like position over the lateral olivary nucleus to become an extended column of cells lying among the fibers of the olivocochlear bundle.

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.

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