Inhibiting the inhibition

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

Decoding neural responses to temporal cues for sound localization

The activity of sensory neural populations carries information about the environment. This may be extracted from neural activity using different strategies. In the auditory brainstem, a recent theory proposes that sound location in the horizontal plane is decoded from the relative summed activity of two populations in each hemisphere, whereas earlier theories hypothesized that the location was decoded from the identity of the most active cells. We tested the performance of various decoders of neural responses in increasingly complex acoustical situations, including spectrum variations, noise, and sound diffraction. We demonstrate that there is insufficient information in the pooled activity of each hemisphere to estimate sound direction in a reliable way consistent with behavior, whereas robust estimates can be obtained from neural activity by taking into account the heterogeneous tuning of cells. These estimates can still be obtained when only contralateral neural responses are used, consistently with unilateral lesion studies. DOI: http://dx.doi.org/10.7554/eLife.01312.001

Population Coding of Interaural Time Differences in Gerbils and Barn Owls

Interaural time differences (ITDs) are the primary cue for the localization of low-frequency sound sources in the azimuthal plane. For decades, it was assumed that the coding of ITDs in the mammalian brain was similar to that in the avian brain, where information is sparsely distributed across individual neurons, but recent studies have suggested otherwise. In this study, we characterized the representation of ITDs in adult male and female gerbils. First, we performed behavioral experiments to determine the acuity with which gerbils can use ITDs to localize sounds. Next, we used different decoders to infer ITDs from the activity of a population of neurons in central nucleus of the inferior colliculus. These results show that ITDs are not represented in a distributed manner, but rather in the summed activity of the entire population. To contrast these results with those from a population where the representation of ITDs is known to be sparsely distributed, we performed the same analysis on activity from the external nucleus of the inferior colliculus of adult male and female barn owls. Together, our results support the idea that, unlike the avian brain, the mammalian brain represents ITDs in the overall activity of a homogenous population of neurons within each hemisphere

Coding of auditory space

Behavioral, anatomical, and physiological approaches can be integrated in the study of sound localization in barn owls. Space representation in owls provides a useful example for discussion of place and ensemble coding. Selectivity for space is broad and ambiguous in low-order neurons. Parallel pathways for binaural cues and for different frequency bands converge on high-order space-specific neurons, which encode space more precisely. An ensemble of broadly tuned place-coding neurons may converge on a single high-order neuron to create an improved labeled line. Thus, the two coding schemes are not alternate methods. Owls can localize sounds by using either the isomorphic map of auditory space in the midbrain or forebrain neural networks in which space is not mapped

Adjustment of interaural-time-difference analysis to sound level

To localize low-frequency sound sources in azimuth, the binaural system compares the timing of sound waves at the two ears with microsecond precision. A similarly high precision is also seen in the binaural processing of the envelopes of high-frequency complex sounds. Both for low- and high-frequency sounds, interaural time difference (ITD) acuity is to a large extent independent of sound level. The mechanisms underlying this level-invariant extraction of ITDs by the binaural system are, however, only poorly understood. We use high-frequency pip trains with asymmetric and dichotic pip envelopes in a combined psychophysical, electrophysiological, and modeling approach. Although the dichotic envelopes cannot be physically matched in terms of ITD, the match produced perceptually by humans is very reliable, and it depends systematically on the overall sound level. These data are reflected in neural responses from the gerbil lateral superior olive and lateral lemniscus. The results are predicted in an existing temporal-integration model extended with a level-dependent threshold criterion. These data provide a very sensitive quantification of how the peripheral temporal code is conditioned for binaural analysis

Adaptation of Binaural Processing in the Adult Brainstem Induced by Ambient Noise

Interaural differences in stimulus intensity and timing are major cues for sound localization. In mammals, these cues are first processed in the lateral and medial superior olive by interaction of excitatory and inhibitory synaptic inputs from ipsi- and contralateral cochlear nucleus neurons. To preserve sound localization acuity following changes in the acoustic environment, the processing of these binaural cues needs neuronal adaptation. Recent studies have shown that binaural sensitivity adapts to stimulation history within milliseconds, but the actual extent of binaural adaptation is unknown. In the current study, we investigated long-term effects on binaural sensitivity using extracellular in vivo recordings from single neurons in the dorsal nucleus of the lateral lemniscus that inherit their binaural properties directly from the lateral and medial superior olives. In contrast to most previous studies, we used a noninvasive approach to influence this processing. Adult gerbils were exposed for 2 weeks to moderate noise with no stable binaural cue. We found monaural response properties to be unaffected by this measure. However, neuronal sensitivity to binaural cues was reversibly altered for a few days. Computational models of sensitivity to interaural time and level differences suggest that upregulation of inhibition in the superior olivary complex can explain the electrophysiological data

Interaural time difference processing in the mammalian medial superior olive

The dominant cue for localization of low-frequency sounds are microsecond differences in the time-of-arrival of sounds at the two ears [interaural time difference (ITD)]. In mammals, ITD sensitivity is established in the medial superior olive (MSO) by coincidence detection of excitatory inputs from both ears. Hence the relative delay of the binaural inputs is crucial for adjusting ITD sensitivity in MSO cells. How these delays are constructed is, however, still unknown. Specifically, the question of whether inhibitory inputs are involved in timing the net excitation in MSO cells, and if so how, is controversial. These inhibitory inputs derive from the nuclei of the trapezoid body, which have physiological and structural specializations for high-fidelity temporal transmission, raising the possibility that well timed inhibition is involved in tuning ITD sensitivity. Here, we present physiological and pharmacological data from in vivo extracellular MSO recordings in anesthetized gerbils. Reversible blockade of synaptic inhibition by iontophoretic application of the glycine antagonist strychnine increased firing rates and significantly shifted ITD sensitivity of MSO neurons. This indicates that glycinergic inhibition plays a major role in tuning the delays of binaural excitation. We also tonically applied glycine, which lowered firing rates but also shifted ITD sensitivity in a way analogous to strychnine. Hence tonic glycine application experimentally decoupled the effect of inhibition from the timing of its inputs. We conclude that, for proper ITD processing, not only is inhibition necessary, but it must also be precisely timed

A physiologically inspired model for solving the cocktail party problem.

At a cocktail party, we can broadly monitor the entire acoustic scene to detect important cues (e.g., our names being called, or the fire alarm going off), or selectively listen to a target sound source (e.g., a conversation partner). It has recently been observed that individual neurons in the avian field L (analog to the mammalian auditory cortex) can display broad spatial tuning to single targets and selective tuning to a target embedded in spatially distributed sound mixtures. Here, we describe a model inspired by these experimental observations and apply it to process mixtures of human speech sentences. This processing is realized in the neural spiking domain. It converts binaural acoustic inputs into cortical spike trains using a multi-stage model composed of a cochlear filter-bank, a midbrain spatial-localization network, and a cortical network. The output spike trains of the cortical network are then converted back into an acoustic waveform, using a stimulus reconstruction technique. The intelligibility of the reconstructed output is quantified using an objective measure of speech intelligibility. We apply the algorithm to single and multi-talker speech to demonstrate that the physiologically inspired algorithm is able to achieve intelligible reconstruction of an "attended" target sentence embedded in two other non-attended masker sentences. The algorithm is also robust to masker level and displays performance trends comparable to humans. The ideas from this work may help improve the performance of hearing assistive devices (e.g., hearing aids and cochlear implants), speech-recognition technology, and computational algorithms for processing natural scenes cluttered with spatially distributed acoustic objects.R01 DC000100 - NIDCD NIH HHSPublished versio

Sensitivity to interaural time differences in the medial superior olive of a small mammal, the Mexican free-tailed bat

Neurons in the medial superior olive (MSO) are thought to encode interaural time differences (ITDs), the main binaural cues used for localizing low-frequency sounds in the horizontal plane. The underlying mechanism is supposed to rely on a coincidence of excitatory inputs from the two ears that are phase-locked to either the stimulus frequency or the stimulus envelope. Extracellular recordings from MSO neurons in several mammals conform with this theory. However, there are two aspects that remain puzzling. The first concerns the role of the MSO in small mammals that have relatively poor low-frequency hearing and whose heads generate only very small ITDs. The second puzzling aspect of the scenario concerns the role of the prominent binaural inhibitory inputs to MSO neurons. We examined these two unresolved issues by recording from MSO cells in the Mexican free-tailed bat. Using sinusoidally amplitude-modulated tones, we found that the ITD sensitivities of many MSO cells in the bat were remarkably similar to those reported for larger mammals. Our data also indicate an important role for inhibition in sharpening ITD sensitivity and increasing the dynamic range of ITD functions. A simple model of ITD coding based on the timing of multiple inputs is proposed. Additionally, our data suggest that ITD coding is a by-product of a neuronal circuit that processes the temporal structure of sounds. Because of the free-tailed bat's small head size, ITD coding is most likely not the major function of the MSO in this small mammal and probably other small mammals