title: Activity-dependent modulation of inhibitory synaptic kinetics in the cochlear nucleus.
abstract: Spherical bushy cells (SBCs) in the anteroventral cochlear nucleus respond to acoustic stimulation with discharges that precisely encode the phase of low-frequency sound. The accuracy of spiking is crucial for sound localization and speech perception. Compared to the auditory nerve input, temporal precision of SBC spiking is improved through the engagement of acoustically evoked inhibition. Recently, the inhibition was shown to be less precise than previously understood. It shifts from predominantly glycinergic to synergistic GABA/glycine transmission in an activity-dependent manner. Concurrently, the inhibition attains a tonic character through temporal summation. The present study provides a comprehensive understanding of the mechanisms underlying this slow inhibitory input. We performed whole-cell voltage clamp recordings on SBCs from juvenile Mongolian gerbils and recorded evoked inhibitory postsynaptic currents (IPSCs) at physiological rates. The data reveal activity-dependent IPSC kinetics, i.e., the decay is slowed with increased input rates or recruitment. Lowering the release probability yielded faster decay kinetics of the single- and short train-IPSCs at 100 Hz, suggesting that transmitter quantity plays an important role in controlling the decay. Slow transmitter clearance from the synaptic cleft caused prolonged receptor binding and, in the case of glycine, spillover to nearby synapses. The GABAergic component prolonged the decay by contributing to the asynchronous vesicle release depending on the input rate. Hence, the different factors controlling the amount of transmitters in the synapse jointly slow the inhibition during physiologically relevant activity. Taken together, the slow time course is predominantly determined by the receptor kinetics and transmitter clearance during short stimuli, whereas long duration or high frequency stimulation additionally engage asynchronous release to prolong IPSCs.
authors.affiliation: Department of Neurobiology, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig Leipzig, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Nerlich
authors.affiliation: Department of Neurobiology, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig Leipzig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Keine
authors.affiliation: Department of Neurobiology, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig Leipzig, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Rübsamen
authors.affiliation: Department of Biological Sciences, Lehigh University Bethlehem, PA, USA.
authors.forename: R Michael
authors.initials: RM
authors.lastname: Burger
authors.affiliation: Department of Physiology, Faculty of Medicine, Carl Ludwig Institute for Physiology, University of Leipzig Leipzig, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Milenkovic
mesh_terms: D000818:Animals; D017626:Cochlear Nucleus / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D005849:Gerbillinae; D005998:Glycine / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid; D005998:Glycine
keywords: activity-dependent decay; asynchronous release; cochlear nucleus; inhibition; intersynaptic pooling; re-uptake; spherical bushy cell