title: Slow Cholinergic Modulation of Spike Probability in Ultra-Fast Time-Coding Sensory Neurons.
abstract: 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 applicationin vitroandin 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 outputin 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.
authors.affiliation: Institute for Biology II, Department of Zoology/Animal Physiology, RWTH Aachen University , D-52074 Aachen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Goyer
authors.affiliation: Institute for Biology II, Department of Zoology/Animal Physiology, RWTH Aachen University , D-52074 Aachen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kurth
authors.affiliation: Institute for Biology II, Department of Zoology/Animal Physiology, RWTH Aachen University , D-52074 Aachen, Germany.
authors.forename: Charlène
authors.identifier: 0000-0002-4448-1200
authors.initials: C
authors.lastname: Gillet
authors.affiliation: Institute of Biology, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig , D-04103 Leipzig, Germany.
authors.forename: Christian
authors.identifier: 0000-0002-8953-2593
authors.initials: C
authors.lastname: Keine
authors.affiliation: Institute of Biology, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig , D-04103 Leipzig, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Rübsamen
authors.affiliation: Institute for Biology II, Department of Zoology/Animal Physiology, RWTH Aachen University , D-52074 Aachen, Germany.
authors.forename: Thomas
authors.identifier: 0000-0003-0993-8524
authors.initials: T
authors.lastname: Kuenzel
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D003198:Computer Simulation; D005849:Gerbillinae; D008959:Models, Neurological; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D018678:Cholinergic Agents; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D002217:Carbachol; D000109:Acetylcholine
keywords: acetylcholine ; anteroventral cochlear nucleus; gerbil; meriones unguiculatus; olivocochlear bundle; spherical bushy cell