TY - JOUR T1 - Slow Cholinergic Modulation of Spike Probability in Ultra-Fast Time-Coding Sensory Neurons JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0186-16.2016 VL - 3 IS - 5 SP - ENEURO.0186-16.2016 AU - David Goyer AU - Stefanie Kurth AU - Charlène Gillet AU - Christian Keine AU - Rudolf Rübsamen AU - Thomas Kuenzel Y1 - 2016/09/01 UR - http://www.eneuro.org/content/3/5/ENEURO.0186-16.2016.abstract N2 - 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 nonauditory 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 (SBCs) 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 SBCs 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. ER -