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Neuronal inhibition is crucial for temporally precise and reproducible signaling in the auditory brainstem. We showed previously (Keine et al., 2016) that for various synthetic stimuli, spherical bushy cell (SBC) activity in the Mongolian gerbil is rendered sparser and more reliable by subtractive inhibition. Employing environmental stimuli, we demonstrate here that the inhibitory gain control becomes even more effective, keeping stimulated response rates equal to spontaneous ones. However, what are the costs of this modulation? We performed dynamic stimulus reconstructions based on neural population responses for auditory nerve (ANF) input and SBC output to assess the influence of inhibition on signal representation. Compared to ANFs, reconstructions of natural stimuli based on SBC responses were temporally more precise, but the match between acoustic and represented signal decreased. Hence, for natural sounds, inhibition at SBCs plays an even stronger role in achieving sparse and reproducible neuronal activity, while compromising general signal representation., This article has been published in eLife on September 25, 2017 [DOI: 10.7554/eLife.29639]

GABA and glycine are the major inhibitory transmitters that attune neuronal activity in the CNS of mammals. The respective transmitters are mostly spatially separated, that is, synaptic inhibition in the forebrain areas is mediated by GABA, whereas glycine is predominantly used in the brainstem. Accordingly, inhibition in auditory brainstem circuits is largely mediated by glycine, but there are few auditory synapses using both transmitters in maturity. Little is known about physiological advantages of such a two-transmitter inhibitory mechanism. We explored the benefit of engaging both glycine and GABA with inhibition at the endbulb of Held-spherical bushy cell synapse in the auditory brainstem of juvenile Mongolian gerbils. This model synapse enables selectivein vivoactivation of excitatory and inhibitory neuronal inputs through systemic sound stimulation and precise analysis of the input (endbulb of Held) output (spherical bushy cell) function. The combination ofin vivoand slice electrophysiology revealed that the dynamic AP inhibition in spherical bushy cells closely matches the inhibitory conductance profile determined by the glycine-R and GABAA-R. The slow and potent glycinergic component dominates the inhibitory conductance, thereby primarily accounting for its high-pass filter properties. GABAergic transmission enhances the inhibitory strength and shapes its duration in an activity-dependent manner, thus increasing the inhibitory potency to suppress the excitation through the endbulb of Held. Finally,in silicomodeling provides a strong link betweenin vivoand slice data by simulating the interactions between the endbulb- and the synergistic glycine-GABA-conductances duringin vivo-like spontaneous and sound evoked activities.