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Graphical abstract Highlights • Stimulation of a hearing ear activates the cochlear nucleus on the opposite deafened side. • Stimulation of a deaf ear fails to activate the contralateral undeprived cochlear nucleus. • Single-sided deafness results in loss of tonotopy along the deprived auditory pathway only. • Binaural stimulation of a single-sided deafened system decreases neuronal activity compared to unilateral stimulation. • Electric and/or acoustic stimulation of hearing rats induces equivalent local activation of auditory neurons. Abstract Worldwide, almost 500 million people are hearing impaired, making hearing loss the most common sensory impairment among humans. For people with single-sided deafness (SSD), cochlear implants (CIs) can be enormously beneficial by providing binaural information. However, binaural benefits in CI users have been only incompletely realized. Overcoming these limitations requires a better knowledge of how neuronal circuits adapt to SSD and how unilateral CI stimulation can compensate a deaf ear. We investigated effects of neonatal SSD on auditory brainstem circuitry using acoustic (AS), electric (ES), or acoustic stimulation on one ear and electric stimulation on the other ear (AS + ES). The molecular marker Fos was used to investigate changes in interneuronal communication due to SSD. To induce SSD, neonatal rats obtained a unilateral intracochlear injection of neomycin. In adulthood, rats were acutely stimulated by AS, ES, or AS + ES. AS and ES were applied correspondingly in terms of intracochlear stimulation side and intensity resulting in bilaterally comparable Fos expression in hearing rats. In contrast, SSD rats showed a loss of tonotopic order along the deafened pathway, indicated by a massive increase and spread of Fos expressing neurons. We report three major results: First, AS of the hearing ear of SSD rats resulted in bilateral activation of neurons in the cochlear nucleus (CN). Second, ES of the deaf ear did not activate contralateral CN. Third, AS + ES of SSD rats resulted in bilateral reduced Fos expression in the auditory brainstem compared to monaural stimulations. These findings indicate changes in inhibitory interactions among neuronal networks as a result of monaural deafness. [ABSTRACT FROM AUTHOR]