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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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In the auditory system, large somatic synapses convey strong excitation that supports temporally precise information transfer. The information transfer of such synapses has predominantly been investigated in the endbulbs of Held in the anterior ventral cochlear nucleus and the calyx of Held in the medial nucleus of the trapezoid body. These large synapses either work as relays or integrate over a small number of inputs to excite the postsynaptic neuron beyond action potential (AP) threshold. In the monaural system, another large somatic synapse targets neurons in the ventral nucleus of the lateral lemniscus (VNLL). Here, we comparatively analyze the mechanisms of synaptic information transfer in endbulbs in the VNLL and the calyx of Held in juvenile Mongolian gerbils. We find that endbulbs in the VNLL are functionally surface-scaled versions of the calyx of Held with respect to vesicle availability, release efficacy, and synaptic peak currents. This functional scaling is achieved by different calcium current kinetics that compensate for the smaller AP in VNLL endbulbs. However, the average postsynaptic current in the VNLL fails to elicit APs in its target neurons, even though equal current suffices to generate APs in neurons postsynaptic to the calyx of Held. In the VNLL, a postsynaptic A-type outward current reduces excitability and prevents AP generation upon a single presynaptic input. Instead, coincidence detection of inputs from two converging endbulbs is ideal to reliably trigger APs. Thus, even large endbulbs do not guarantee one-to-one AP transfer. Instead, information flow appears regulated by circuit requirements.

The dorsal nucleus of the lateral lemniscus (DNLL) is an auditory brain stem structure that generates a long-lasting GABAergic output, which is important for binaural processing. Despite its importance in binaural processing, little is known about the cellular physiology and the synaptic input kinetics of DNLL neurons. To assess the relevant physiological parameters of DNLL neurons, their late postnatal developmental profile was analyzed in acute brain slices of 9- to 26-day-old Mongolian gerbils. The observed developmental changes in passive membrane and action potential (AP) properties all point toward an improvement of fast and precise signal integration in these neurons. Accordingly, synaptic glutamatergic and GABAergic current kinetics accelerate with age. The changes in intrinsic and synaptic properties contribute nearly equally to reduce the latency and jitter in AP generation and thus enhance the temporal precision of DNLL neurons. Furthermore, the size of the synaptic NMDA current is developmentally downregulated. Despite this developmental reduction, DNLL neurons display an NMDA-dependent postsynaptic amplification of AP generation, known to support high firing rates, throughout this developmental period. Taken together, our findings indicate that during late postnatal development DNLL neurons are optimized for high firing rates with high temporal precision.