Reconnecting neuronal networks in the auditory brainstem following unilateral deafening.

When we disturbed the auditory input of the adult rat by cochleotomy or noise trauma on one side, several substantial anatomical, cellular, and molecular changes took place in the auditory brainstem. We found that: (1) cochleotomy or severe noise trauma both lead to a considerable increase of immunoreactivity of the growth-associated protein GAP-43 in the ventral cochlear nucleus (VCN) of the affected side; (2) the expression of GAP-43 in VCN is restricted to presynaptic endings and short fiber segments; (3) axon collaterals of the cholinergic medial olivocochlear (MOC) neurons are the path along which GAP-43 reaches VCN; (4) partial cochlear lesions induce the emergence of GAP-43 positive presynaptic endings only in regions tonotopically corresponding to the extent of the lesion; (5) judging from the presence of immature fibers and growth cones in VCN on the deafened side, at least part of the GAP-43 positive presynaptic endings appear to be newly formed neuronal contacts following axonal sprouting while others may be modified pre-existing contacts; and (6) GAP-43 positive synapses are formed only on specific postsynaptic profiles, i.e., glutamatergic, glycinergic and calretinin containing cell bodies, but not GABAergic cell bodies. We conclude that unilateral deafening, be it partial or total, induces complex patterns of reconnecting neurons in the adult auditory brainstem, and we evaluate the possibility that the deafness-induced chain of events is optimized to remedy the loss of a bilaterally balanced activity in the auditory brainstem.

Transcription factor modulation and expression in the rat auditory brainstem following electrical intracochlear stimulation.

Neuronal activity in sensory organs elicited by adequate or electrical stimulation not only invokes fast electrical responses but may also trigger complex molecular changes inside central neurons. Following electrical intracochlear stimulation with a cochlear implant under urethane anesthesia, we observed changes in the phosphorylation state of the cAMP response element binding protein (CREB) and the expression of the immediate-early genes c-fos and egr-1, molecules known to act as transcription factors, in a tonotopically precise pattern in central auditory neurons. These neurons resided in the posteroventral and anteroventral cochlear nucleus, the dorsal cochlear nucleus, the lateral superior olive, the medial nucleus of the trapezoid body, the dorsal and ventral nucleus of the lateral lemniscus, and the central nucleus of the inferior colliculus. Moreover, effects of electrical stimulation were identified in the medial vestibular nucleus and the lateral parabrachial nucleus. Regionally, CREB was dephosphorylated wherever immediate-early gene expression went up. These massive stimulation-dependent modulations of transcription factors in the ascending auditory system are indicative of ongoing changes that modify the chemistry and structure of the affected cells and, consequently, their response characteristics to subsequent stimulation of the inner ear.