Temporal processing capacity in auditory-deprived superior paraolivary neurons is rescued by sequential plasticity during early development

- Streaming of temporal acoustic cues is conveyed by rebound spiking in SPON.
- Congenitally deaf mice have imprecise rebound spiking in SPON compared to controls during early postnatal development.
- Sequential regulation of ion currents underlying the rebound spiking mechanism rescues and normalizes the SPON output.
- This stereotyped neuronal compensation could be key for success of auditory prostheses.

The leading treatments for severe hearing disabilities work on the principle of conveying electrical pulses to the auditory brainstem that enable perception of speech. It is currently not known how well the brainstem neurons specialized for decoding such coarse sound information develop when deprived of auditory input activity. Here, we used congenitally deaf α1D−/− mice, lacking activity in the auditory nerve, to investigate the superior paraolivary nucleus (SPON) - a prominent mammalian brainstem structure that responds selectively to sound pulses by rebound spiking. Whole-cell patch-clamp recordings from SPON neurons in the α1D−/− and control mice were obtained at equivalent pre- and post-hearing onset ages. The results show that SPON neurons in the α1D−/− display less precise, plateau-like rebound spiking compared to control neurons. However, the rebound spiking mechanism undergoes strong compensation with age in the α1D−/−. Voltage-activated Ca2+-currents lower the spike threshold, rescuing the capacity for spike initiation at pre-hearing onset ages. Gradual up-regulation of the inwardly rectifying h-current contributes to depolarize the membrane potential. Reduction of the membrane time constant and less recruitment of Ca2+-currents thereby normalize precise rebound spiking at post-hearing onset ages. We found the soluble form of the neurotrophic factor neuritin to be up-regulated in SPON of deaf mice, which may have promoted neuronal survival and prolonged plasticity of the SPON circuitry. A stereotyped timeline of compensation of rebound spiking in deaf SPON neurons indicates robust intrinsic regulation of the brainstem circuitry encoding sound rhythms. This may be a prerequisite for successful cochlear implants.