No abstract

Expression of the growth and plasticity associated protein GAP‐43 is closely related to synaptogenesis and synaptic remodeling in the developing as well as in the mature nervous system. We have studied the postnatal development of GAP‐43 mRNA expression in the auditory brainstem and determined the time course of its reexpression following deafening through cochlear ablation using a digoxigenin‐coupled mRNA probe. By the first postnatal day, GAP‐43 mRNA was expressed at high levels in all auditory brainstem nuclei. But whereas GAP‐43 mRNA is almost entirely lost in most of these nuclei in the adult animal, significant levels of this molecule are retained in the inferior colliculus and, most notably, in the lateral and medial superior olivary nucleus. As a consequence of unilateral cochleotomy, GAP‐43 mRNA rose dramatically in some neurons of the ipsilateral lateral superior olive, whereas the hybridization signal decreased in others. Using double staining protocols, we found that those olivary neurons that increase their level of GAP‐43 mRNA appear to be identical with the cells developing strong GAP‐43 immunoreactivity after cochleotomy. By combining axonal tracing with in situ hybridization, we proved that at least some of the cells with increased levels of GAP‐43 mRNA and protein are the cells of origin of olivocochlear projections. A substantial decrease of the level of GAP‐43 mRNA took place in the inferior colliculus contralateral to the lesioned cochlea. Our results led us to suggest that neurons in the superior olivary complex may play a crucial role in orchestrating auditory brainstem plasticity. J. Comp. Neurol. 412:353–372, 1999. © 1999 Wiley‐Liss, Inc.

Extensive data link the growth associated protein GAP-43 to axonal elongation and synapse formation during development and in plastic responses of nervous tissue. We have studied the changing levels of GAP-43 expression in the auditory brainstem nuclei of the developing rat by applying immunocytochemical techniques. By the first postnatal day (P1), GAP-43 was expressed at high concentrations in all subdivisions of the cochlear nuclear complex and the superior olivary complex. At this stage, neuropil structures recognized by the antibody did not show any varicosities on cellular processes in all these regions. By P8, the texture of the stain has turned markedly more granular, a pattern likely to reflect the formation of presynaptic endings. A predominantly granular distribution of GAP-43 has developed by P12. At that time, the staining intensity is markedly reduced compared to the levels of the newborn. By P16, the auditory brainstem nuclei have lost most of their GAP-43 immunoreactivity, but a distinct level of staining persisted into adulthood in all of them. This staining was restricted to boutons, which are thought to be presynaptic terminals. We conclude that a moderate but apparently relevant potential for plasticity is retained in these auditory structures. Should the patterns of neural signals, mediated by the inner ear, change during adulthood, the central structures appear to be able to respond with the formation of altered synaptic connectivity.