title: Activity-dependent transmission and integration control the timescales of auditory processing at an inhibitory synapse.
abstract: To capture the context of sensory information, neural networks must process input signals across multiple timescales. In the auditory system, a prominent change in temporal processing takes place at an inhibitory GABAergic synapse in the dorsal nucleus of the lateral lemniscus (DNLL). At this synapse, inhibition outlasts the stimulus by tens of milliseconds, such that it suppresses responses to lagging sounds, and is therefore implicated in echo suppression. Here, we untangle the cellular basis of this inhibition. We demonstrate with in vivo whole-cell patch-clamp recordings in Mongolian gerbils that the duration of inhibition increases with sound intensity. Activity-dependent spillover and asynchronous release translate the high presynaptic firing rates found in vivo into a prolonged synaptic output in acute slice recordings. A key mechanism controlling the inhibitory time course is the passive integration of the hyperpolarizing inhibitory conductance. This prolongation depends on the synaptic conductance amplitude. Computational modeling shows that this prolongation is a general mechanism and relies on a non-linear effect caused by synaptic conductance saturation when approaching the GABA reversal potential. The resulting hyperpolarization generates an efficient activity-dependent suppression of action potentials without affecting the threshold or gain of the input-output function. Taken together, the GABAergic inhibition in the DNLL is adjusted to the physiologically relevant duration by passive integration of inhibition with activity-dependent synaptic kinetics. This change in processing timescale combined with the reciprocal connectivity between the DNLLs implements a mechanism to suppress the distracting localization cues of echoes and helps to localize the initial sound source reliably.
authors.affiliation: Division of Neurobiology, Department Biology II, Ludwig-Maximilians University Munich, Großhaderner Straße 2, 82152 Planegg-Martinsried, Germany; Graduate School of Systemic Neuroscience Munich, 82152 Planegg-Martinsried, Germany.
authors.forename: Julian J
authors.initials: JJ
authors.lastname: Ammer
authors.affiliation: Division of Neurobiology, Department Biology II, Ludwig-Maximilians University Munich, Großhaderner Straße 2, 82152 Planegg-Martinsried, Germany.
authors.forename: Ida
authors.initials: I
authors.lastname: Siveke
authors.affiliation: Division of Neurobiology, Department Biology II, Ludwig-Maximilians University Munich, Großhaderner Straße 2, 82152 Planegg-Martinsried, Germany; Bioimaging Center, Department Biology I, Ludwig-Maximilians University Munich, Großhaderner Straße 2, 82152 Planegg-Martinsried, Germany. Electronic address: felmy@zi.biologie.uni-muenchen.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Felmy
mesh_terms: D000200:Action Potentials; D000818:Animals; D001306:Auditory Pathways; D016764:Cell Polarity; D005849:Gerbillinae; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid