gms | German Medical Science

76th Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

04.05. - 08.05.2005, Erfurt

Expression of the plasticity marker c-Fos in auditory brainstem projection neurons of the rat after electrical intacochlear stimulation

Meeting Abstract

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  • corresponding author Adrian Reisch - Universitäts-HNO-Klinik Neurobiologisches Forschungslabor, Freiburg, Germany
  • author Robert-Benjamin Illing - Universitäts-HNO-Klinik Neurobiologisches Forschungslabor, Freiburg, Germany
  • Roland Laszig - Universitäts-HNO-Klinik, Freiburg, Germany

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. 76. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V.. Erfurt, 04.-08.05.2005. Düsseldorf, Köln: German Medical Science; 2005. Doc05hno563

The electronic version of this article is the complete one and can be found online at:

Published: September 22, 2005

© 2005 Reisch et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Cochlear implants (CI) are a powerful tool to restore auditory input to the brain by direct electrical stimulation of the auditory nerve after deafness caused by the degeneration of the cochlear hair cells. Stimulation-mediated neuronal activity may trigger molecular changes via complex intracellular signaling cascades in which the transcription factor c-Fos is involved. Expression of c-Fos has been observed in central auditory neurons of various regions after acoustic or electrical stimulation of the ear upon the processing of novel stimuli in the sense of a learning process. So far it is not known how this exactly works, not even which neurons respond with an upregulated c-Fos expression to the changed sensory activation. To understand how unilaterally changed activity is processed by the brain it is a necessary step to find out if every cell is affected or if only distinct subpopulations respond to the stimulation.

We investigated this activity dependent plasticity of auditory neurons in a rat model system, focusing on the nuclei of the auditory brainstem. C-Fos expressing cells in the anteroventral cochlear nucleus (AVCN), the lateral superior olive (LSO) and the colliculus inferior (IC) were characterized by the neurotransmitter they use and by the area to which they send their axon. Electrical intracochlear stimulation (EIS) was applied unilaterally in acute experiments for 2h under urethane anesthesia. The tip electrodes of a cochlear implant Type-CI24M, kindly provided by Cochlear AG Basel, Switzerland were inserted into the basal turn of the cochlea and it was aimed to obtain an initial electrically evoked maximal brainstem response amplitude in the range of 5-8 μV. To reduce adaptation of the auditory system to the stimulation, 30 sec of stimulation alternated with 30 sec pause. Seven to ten days before stimulation, fluorescence tracers were injected into the VCN contralateral to the stimulation site or into the IC either ipsilateral or contralateral to EIS. Immediately after EIS, the animals were transcardially perfused with fixative solution and the brain was cut into frontal sections. After incubation for 48h with primary antibody, the binding sites were visualized with matching fluorescence labeled secondary antibodies.

EIS induced expression of c-Fos only in neurons corresponding tonotopically to the intracochlear stimulation in the AVCN (Fig. 1), LSO and IC. We found that about 50% of c-Fos positive nuclei belonged to glutamatergic neurons (Fig. 2A) and about 50% to glycinergic cells (Fig. 2B) in both the anteroventral cochlear nucleus and in the lateral superior olive ipsilateral to the stimulation. In the colliculus inferior on the contralateral site about 45% of c-Fos positive nuclei belonged to glutamatergic cells and about 30% to glycinergic neurons. GABAergic cells seem not to respond to the stimulation with upregulation of c-Fos in either region (Fig. 2C). Remarkably, c-Fos is strongly expressed in neurons of the AVCN projecting to the inferior colliculus, but only rarely in cells of the LSO with the same target region.

We conclude that only distinct subpopulations of neurons responds to EIS with expression of the transcription factor c-Fos, suggesting that these cells preferentially undergo plastic changes upon changes in neuronal activity as induced in our experiments. Interestingly, not only excitatory cells processing signals along the ascending auditory branch express c-Fos upon stimulation, but also inhibitory neurons using glycin as neurotransmitter projecting from the AVCN to the contralateral VCN and to the ipsilateral IC. The massive c-Fos upregulation after unilateral stimulation in these inhibitory might indicate, that the system tends toward rebalancing of activity between ipsi- and contralateral part following unilateral hearing impairment.

Supported by: DFG, GRK 843