One of the hallmarks of auditory neurons in vivo is spontaneous activity that occurs even in the absence of any sensory stimuli. Sound-evoked bursts of discharges are thus embedded within this background of random firing. The calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) has been characterized in vitro as a fast relay that reliably fires at high stimulus frequencies (< or =800 Hz). However, inherently due to the preparation method, spontaneous activity is absent in studies using brain stem slices. Here we first determine in vivo spontaneous firing rates of MNTB principal cells from Mongolian gerbils and then reintroduce this random firing to in vitro gerbil brain stem synapses at near-physiological temperature. After conditioning synapses with afferent fiber stimulation for 2 min at Poisson averaged rates of 20, 40, and 60 Hz, we observed a number of differences in the properties of synaptic transmission between conditioned and unconditioned synapses. Foremost, we observed reduced steady-state EPSC amplitudes that depressed even further during an embedded short-stimulation train of 100, 300, or 600 Hz (a protocol that thus simulates in vitro what probably occurs at the in vivo MNTB after a short sound stimulus in a silent background). Accordingly, current-clamp, dynamic-clamp, and loose-patch recordings revealed a number of action potential failures at the postsynaptic cell during high-frequency-stimulation trains, although the initial onset of evoked activity was still transmitted with higher fidelity. We thus propose that some in vivo auditory synapses are in a tonic state of reduced EPSC amplitudes as a consequence of high spontaneous spiking and this in vivo-like conditioning has important consequences for the encoding of signals throughout the auditory pathway.

Here we show that inhibition shapes diverse responses to species-specific calls in the inferior colliculus (IC) of Mexican free-tailed bats. We presented 10 calls to each neuron of which 8 were social communication and 2 were echolocation calls. We also measured excitatory response regions: the range of tone burst frequencies that evoked discharges at a fixed intensity. The calls evoked highly selective responses in that IC neurons responded to some calls but not others even though those calls swept through their excitatory response regions. By convolving activity in the response regions with the spectrogram of each call, we evaluated whether responses to tone bursts could predict discharge patterns evoked by species-specific calls. The convolutions often predicted responses to calls that evoked no responses and thus were inaccurate. Blocking inhibition at the IC reduced or eliminated selectivity and greatly improved the predictive accuracy of the convolutions. By comparing the responses evoked by two calls with similar spectra, we show that each call evoked a unique spatiotemporal pattern of activity distributed across and within isofrequency contours and that the disparity in the population response was greatly reduced by blocking inhibition. Thus the inhibition evoked by each call can shape a unique pattern of activity in the IC population and that pattern may be important for both the identification of a particular call and for discriminating it from other calls and other signals.

The precedence effect describes the phenomenon whereby echoes are spatially fused to the location of an initial sound by selectively suppressing the directional information of lagging sounds (echo suppression). Echo suppression is a prerequisite for faithful sound localization in natural environments but can break down depending on the behavioral context. To date, the neural mechanisms that suppress echo directional information without suppressing the perception of echoes themselves are not understood. We performed in vivo recordings in Mongolian gerbils of neurons of the dorsal nucleus of the lateral lemniscus (DNLL), a GABAergic brainstem nucleus that targets the auditory midbrain, and show that these DNLL neurons exhibit inhibition that persists tens of milliseconds beyond the stimulus offset, so-called persistent inhibition (PI). Using in vitro recordings, we demonstrate that PI stems from GABAergic projections from the opposite DNLL. Furthermore, these recordings show that PI is attributable to intrinsic features of this GABAergic innervation. Implementation of these physiological findings into a neuronal model of the auditory brainstem demonstrates that, on a circuit level, PI creates an enhancement of responsiveness to lagging sounds in auditory midbrain cells. Moreover, the model revealed that such response enhancement is a sufficient cue for an ideal observer to identify echoes and to exhibit echo suppression, which agrees closely with the percepts of human subjects.

Our data indicate that cessation of electrical activity after peripheral lesion contributes to the regenerative response observed upon conditioning and might be necessary to promote regeneration after central nervous system injury.