Sensory processing in the lower auditory pathway is generally considered to be rigid and thus less subject to modulation than central processing. However, in addition to the powerful bottom-up excitation by auditory nerve fibers, the ventral cochlear nucleus also receives efferent cholinergic innervation from both auditory and non-auditory top-down sources. We thus tested the influence of cholinergic modulation on highly-precise time-coding neurons in the cochlear nucleus of the Mongolian gerbil. By combining electrophysiological recordings with pharmacological application in vitro and in vivo, we found 55-72% of spherical bushy cells (SBC) to be depolarized by carbachol on two time scales, ranging from hundreds of milliseconds to minutes. These effects were mediated by nicotinic and muscarinic acetylcholine receptors, respectively. Pharmacological block of muscarinic receptors hyperpolarized the resting membrane potential, suggesting a novel mechanism of setting the resting membrane potential for SBC. The cholinergic depolarization led to an increase of spike probability in SBC without compromising the temporal precision of the SBC output in vitro. In vivo, iontophoretic application of carbachol resulted in an increase in spontaneous SBC activity. The inclusion of cholinergic modulation in an SBC model predicted an expansion of the dynamic range of sound responses and increased temporal acuity. Our results thus suggest of a top-down modulatory system mediated by acetylcholine which influences temporally precise information processing in the lower auditory pathway.
Significance Statement Information processing in sensory neural pathways close to the periphery is generally considered to be rigid and therefore less subject to modulation. Here we demonstrate slow cholinergic modulation of information processing in a circuit traditionally seen as a fast and faithful auditory relay station. We combined electrophysiological recordings in vitro and in vivo with pharmacology and computer modeling to show that the excitability of auditory time-coding neurons is increased by the cholinergic modulation. In-vitro recordings indicate that the temporal acuity of the time-coding neurons is maintained. This study thus adds a novel component to the understanding of bottom-up dominated sensory circuitry.
Authors report no conflict of interest
This work was supported by the priority program 1608 “Ultra-fast and temporally precise information processing: Normal and dysfunctional hearing” of the German Research Foundation (DFG) KU2529/2-1 (T.K. & D.G.), KU2529/22 (T.K. & C.G.), RU390/19-1 (R.R. & C.K.) and RU390/20-1 (R.R. & C.K.)