Plasticity of the auditory brainstem: cochleotomy-induced changes of calbindin-D28k expression in the rat.

Calbindin is a calcium binding protein that is characteristically expressed in several auditory brainstem nuclei during ontogeny and is thought to serve as a buffer, protecting cells against toxic levels of calcium. Upon maturation, calbindin is drastically reduced or entirely lost in many auditory nuclei. We made cochleotomies in mature rats to study effects of deafening and deafferentation on the expression of calbindin in the auditory brainstem. Following unilateral cochleotomy, we observed a substantial increase in the number of calbindin-immunoreactive fibers and boutons in the ventral subdivisions of the ipsilateral cochlear nucleus. At the same time, calbindin-positive astrocytes emerged in the dorsal and ventral cochlear nucleus. Beyond the immediately affected ipsilateral cochlear nucleus, we found calbindin-positive neurons in the lateral superior olive and in the central inferior colliculus, both contralateral to the operation. The loss of one cochlea reduces auditory input and puts the flow of neuronal activity originating in the two ears out of balance. Our findings indicate that the need for the neuronal networks in the auditory brainstem to adjust to this drastically changed pattern of sensory signals invokes the expression of calbindin in glial cells as well as in directly and indirectly affected neuronal cell populations.

Auditory brainstem: development and plasticity of GAP-43 mRNA expression in the rat.

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.

Redistribution of NMDA receptors in the cochlear nucleus following cochleotomy.

The major input to neurons of the cochlear nucleus comes from the glutamatergic cells of the spiral ganglion. We have studied the effect of unilateral destruction of the inner ear, including the spiral ganglion, with two antibodies against different types of NMDA receptor subunits, NMDAR1 and NMDAR2A/B, in the cochlear nucleus of the rat. Following cochleotomy, a dramatic redistribution of the receptor subunits was observed from a mostly perikaryal to a predominantly dendritic localization. Moreover, distinct changes in the composition of NMDA receptor complexes occurred. These effects were interpreted as compensatory responses to the massive loss of presynaptic release of the transmitter glutamate.

Evaluating the plasticity potential of the auditory brain stem nucleus in the rat.

OBJECTIVE: To study the adaptation of the auditory brainstem to auditory loss. STUDY DESIGN: Growth-associated protein 43 (GAP-43) immunoreactivity was studied in in rats whose cochleas had been removed. RESULTS AND DISCUSSION: Neurons in the lateral superior olive were found to synthesize GAP-43 in a pattern that paralleled the changes in GAP-43 immunoreactivity in the cochlear nucleus after cochlear ablation. These findings suggest that new patterns of synaptic communication can be established after damage to the cochlea.

Postnatal development of GAP-43 immunoreactivity in the auditory brainstem of the rat.

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.