title: Dynamic fidelity control to the central auditory system: synergistic glycine/GABAergic inhibition in the cochlear nucleus.
abstract: 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 selective in vivo activation 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 of in vivo and 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 silico modeling provides a strong link between in vivo and slice data by simulating the interactions between the endbulb- and the synergistic glycine-GABA-conductances during in vivo-like spontaneous and sound evoked activities.
authors.affiliation: Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Nerlich
authors.affiliation: Institute of Biology 2, RWTH Aachen University, 52062 Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuenzel
authors.affiliation: Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Keine
authors.affiliation: Centre for Laser Microscopy, Department of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia, and.
authors.forename: Andrej
authors.initials: A
authors.lastname: Korenic
authors.affiliation: Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Rübsamen
authors.affiliation: Carl Ludwig Institute for Physiology, Faculty of Medicine, University of Leipzig, 04103 Leipzig, Germany Ivan.Milenkovic@medizin.uni-leipzig.de.
authors.forename: Ivan
authors.initials: I
authors.lastname: Milenkovic
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001306:Auditory Pathways / Q000502:physiology; D001307:Auditory Perception / Q000502:physiology*; D017626:Cochlear Nucleus / Q000378:metabolism*; D005260:Female; D005849:Gerbillinae; D005998:Glycine / Q000378:metabolism*; D008297:Male; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D005998:Glycine
keywords: AP inhibition; GABAA/glycine receptors; auditory signal processing; in vivo electrophysiology; modeling; slice electrophysiology