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The current study examines the modulation of the motion-onset response based on the frequency-range of sound stimuli. Delayed motion-onset and stationary stimuli were presented in a free-field by sequentially activating loudspeakers on an azimuthal plane keeping the natural percept of externalized sound presentation. The sounds were presented in low- or high-frequency ranges and had different motion direction within each hemifield. Difference waves were calculated by contrasting the moving and stationary sounds to isolate the motion-onset responses. Analyses carried out at the peak amplitudes and latencies on the difference waves showed that the early part of the motion response (cN1) was modulated by the frequency range of the sounds with stronger amplitudes elicited by stimuli with high frequency range. Subsequent post hoc analysis of the normalized amplitude of the motion response confirmed the previous finding by excluding the possibility that the frequency range had an overall effect on the waveform, and showing that this effect was instead limited to the motion response. These results support the idea of a modular organization of the motion-onset response with the processing of primary sound motion characteristics being reflected in the early part of the response. Also, the article highlights the importance of specificity in auditory stimulus design.

Inhibition plays a crucial role in neural signal processing, shaping and limiting responses. In the auditory system, inhibition already modulates second order neurons in the cochlear nucleus, e.g. spherical bushy cells (SBCs). While the physiological basis of inhibition and excitation is well described, their functional interaction in signal processing remains elusive. Using a combination of in vivo loose-patch recordings, iontophoretic drug application, and detailed signal analysis in the Mongolian Gerbil, we demonstrate that inhibition is widely co-tuned with excitation, and leads only to minor sharpening of the spectral response properties. Combinations of complex stimuli and neuronal input-output analysis based on spectrotemporal receptive fields revealed inhibition to render the neuronal output temporally sparser and more reproducible than the input. Overall, inhibition plays a central role in improving the temporal response fidelity of SBCs across a wide range of input intensities and thereby provides the basis for high-fidelity signal processing. DOI: http://dx.doi.org/10.7554/eLife.19295.001, eLife digest In humans and other animals, small differences in the time at which a sound arrives at each ear are crucial for determining the location of the sound. Neurons in the first processing station of the brain – the cochlear nucleus – receive information about sounds (or “inputs”) from the ears. They then produce electrical signals that relay this information to other areas of the brain. Some of these inputs increase the activity of the neurons and so are known as “excitatory” inputs, while other “inhibitory” inputs decrease the activity of the neurons. The balance between these two inputs determines what information is passed to other parts of the brain, but it is not clear how these inputs interact. Keine, Rübsamen and Englitz studied electrical activity in the brains of Mongolian gerbils while being exposed to sounds with more natural properties than previously studied. The experiments reveal that inhibitory inputs play an important role in controlling the activity of neurons in the cochlear nucleus. By decreasing the neurons’ activity, inhibitory inputs allow these cells to respond to many different levels of sound, from very loud to very quiet. The experiments also show that excitatory and inhibitory inputs are triggered by similar sounds so that the two processes quickly balance each other. This means that the brain is equally able to work out where a sound is coming from regardless of whether it is loud or quiet. Further work is now needed to understand responses to natural sounds and to determine how experimentally removing the inhibitory inputs affects hearing. DOI: http://dx.doi.org/10.7554/eLife.19295.002

Please find the peer-reviewed publisher version linked below.Signal processing in the auditory brainstem is based on an interaction of neuronal excitation and inhibition. To date, we have incomplete knowledge of how the dynamic interplay of both contributes to the processing power and temporal characteristics of signal coding. The spherical bushy cells (SBCs) of the anteroventral cochlear nucleus (AVCN) receive their primary excitatory input through auditory nerve fibers via large, axosomatic synaptic terminals called the endbulbs of Held and by additional, acoustically driven inhibitory inputs. SBCs provide the input to downstream nuclei of the brainstem sound source localization circuitry, such as the medial and lateral superior olive, which rely on temporal precise inputs. In this study, we used juxtacellular recordings in anesthetized Mongolian gerbils to assess the effect of acoustically evoked inhibition on the SBCs input-output function and on temporal precision of SBC spiking. Acoustically evoked inhibition proved to be strong enough to suppress action potentials (APs) of SBCs in a stimulus-dependent manner. Inhibition shows slow onset and offset dynamics and increasing strength at higher sound intensities. In addition, inhibition decreases the rising slope of the EPSP and prolongs the EPSP-to-AP transition time. Both effects can be mimicked by iontophoretic application of glycine. Inhibition also improves phase locking of SBC APs to low-frequency tones by acting as a gain control to suppress poorly timed EPSPs from generating postsynaptic APs to maintain precise SBC spiking across sound intensities. The present data suggest that inhibition substantially contributes to the processing power of second-order neurons in the ascending auditory system.

Neuronal inhibition is crucial for temporally precise and reproducible signaling in the auditory brainstem. We showed previously (Keine et al., 2016) that for various synthetic stimuli, spherical bushy cell (SBC) activity in the Mongolian gerbil is rendered sparser and more reliable by subtractive inhibition. Employing environmental stimuli, we demonstrate here that the inhibitory gain control becomes even more effective, keeping stimulated response rates equal to spontaneous ones. However, what are the costs of this modulation? We performed dynamic stimulus reconstructions based on neural population responses for auditory nerve (ANF) input and SBC output to assess the influence of inhibition on signal representation. Compared to ANFs, reconstructions of natural stimuli based on SBC responses were temporally more precise, but the match between acoustic and represented signal decreased. Hence, for natural sounds, inhibition at SBCs plays an even stronger role in achieving sparse and reproducible neuronal activity, while compromising general signal representation., This article has been published in eLife on September 25, 2017 [DOI: 10.7554/eLife.29639]

Auditory processing disorder (APD) is defined as a processing deficit in the auditory modality and spans multiple processes. To date, APD diagnosis is mostly based on the utilization of speech material. Adequate nonspeech tests that allow differentiation between an actual central hearing disorder and related disorders such as specific language impairments are still not adequately available. In the present study, 84 children between 6 and 17 years of age (clinical group), referred to three audiological centers for APD diagnosis, were evaluated with standard audiological tests and additional auditory discrimination tests. Latter tests assessed the processing of basic acoustic features at two different stages of the ascending central auditory system: (1) auditory brainstem processing was evaluated by quantifying interaural frequency, level, and signal duration discrimination (interaural tests). (2) Diencephalic/telencephalic processing was assessed by varying the same acoustic parameters (plus signals with sinusoidal amplitude modulation), but presenting the test signals in conjunction with noise pulses to the contralateral ear (dichotic(signal/noise) tests). Data of children in the clinical group were referenced to normative data obtained from more than 300 normally developing healthy school children. The results in the audiological and the discrimination tests diverged widely. Of the 39 children that were diagnosed with APD in the audiological clinic, 30 had deficits in auditory performance. Even more alarming was the fact that of the 45 children with a negative APD diagnosis, 32 showed clear signs of a central hearing deficit. Based on these results, we suggest revising current diagnostic procedure to evaluate APD in order to more clearly differentiate between central auditory processing deficits and higher-order (cognitive and/or language) processing deficits.

Similarities have been observed in the localization of the final position of moving visual and moving auditory stimuli: Perceived endpoints that are judged to be farther in the direction of motion in both modalities likely reflect extrapolation of the trajectory, mediated by predictive mechanisms at higher cognitive levels. However, actual comparisons of the magnitudes of displacement between visual tasks and auditory tasks using the same experimental setup are rare. As such, the purpose of the present free-field study was to investigate the influences of the spatial location of motion offset, stimulus velocity, and motion direction on the localization of the final positions of moving auditory stimuli (Experiment 1 and 2) and moving visual stimuli (Experiment 3). To assess whether auditory performance is affected by dynamically changing binaural cues that are used for the localization of moving auditory stimuli (interaural time differences for low-frequency sounds and interaural intensity differences for high-frequency sounds), two distinct noise bands were employed in Experiments 1 and 2. In all three experiments, less precise encoding of spatial coordinates in paralateral space resulted in larger forward displacements, but this effect was drowned out by the underestimation of target eccentricity in the extreme periphery. Furthermore, our results revealed clear differences between visual and auditory tasks. Displacements in the visual task were dependent on velocity and the spatial location of the final position, but an additional influence of motion direction was observed in the auditory tasks. Together, these findings indicate that the modality-specific processing of motion parameters affects the extrapolation of the trajectory.

In the developing nervous system, spontaneous neuronal activity arises independently of experience or any environmental input. This activity may play a major role in axonal pathfinding, refinement of topographic maps, dendritic morphogenesis, and the segregation of axonal terminal arbors. In the auditory system, endogenously released ATP in the cochlea activates inner hair cells to trigger bursts of action potentials (APs), which are transferred to the central auditory system. Here we show the modulatory role of purinergic signaling beyond the cochlea, i.e., the developmentally regulated and cell-type-specific depolarizing effects on auditory brainstem neurons of Mongolian gerbil. We assessed the effects of P2X receptors (P2XRs) on neuronal excitability from prehearing to early stages of auditory signal processing. Our results demonstrate that in neurons expressing P2XRs, extracellular ATP can evoke APs in sync with Ca(2+) signals. In cochlear nucleus (CN) bushy cells, ATP increases spontaneous and also acoustically evoked activity in vivo, but these effects diminish with maturity. Moreover, ATP not only augmented glutamate-driven firing, but it also evoked APs in the absence of glutamatergic transmission. In vivo recordings also revealed that endogenously released ATP in the CN contributes to neuronal firing activity by facilitating AP generation and prolonging AP duration. Given the enhancing effect of ATP on AP firing and confinement of P2XRs to certain auditory brainstem nuclei, and to distinct neurons within these nuclei, it is conceivable that purinergic signaling plays a specific role in the development of neuronal brainstem circuits.

Motion perception can be altered by information received through multiple senses. So far, the interplay between the visual and the auditory modality in peripheral motion perception is scarcely described. The present free-field study investigated audio-visual motion perception for different azimuthal trajectories in space. To disentangle effects related to crossmodal interactions (the influence of one modality on signal processing in another modality) and multisensory integration (binding of bimodal streams), we manipulated the subjects' attention in two experiments on a single set of moving audio-visual stimuli. Acoustic and visual signals were either congruent or spatially and temporally disparate at motion offset. (i) Crossmodal interactions were studied in a selective attention task. Subjects were instructed to attend to either the acoustic or the visual stream and to indicate the perceived final position of motion. (ii) Multisensory integration was studied in a divided attention task in which subjects were asked to report whether they perceived unified or separated audio-visual motion offsets. The results indicate that crossmodal interactions in motion perception do not depend on the integration of the audio-visual stream. Furthermore, in the crossmodal task, both visual and auditory motion perception were susceptible to modulation by irrelevant streams, provided that temporal disparities did not exceed a critical range. Concurrent visual streams modulated auditory motion perception in the central field, whereas concurrent acoustic streams attracted visual motion information in the periphery. Differential abilities between the visual and auditory system when attempting to accurately track positional information along different trajectories account for the observed biasing effects.

The development of the auditory system has received increasing attention since the mechanisms of patterned, spontaneous activity in prehearing mammals were discovered. This early activity originates in the cochlea and is assumed to be of importance for the establishment and refinement of synaptic connections in the auditory system. In the present study we investigate synaptic transmission and its interplay with spontaneous discharges in the developing auditory system. We used the calyx of Held as a model system, where this question can be investigatedin vivoover a broad range of ages [postnatal day 8 (P8)–P28]. To precisely quantify the timing and reliability of synaptic transmission, we developed a novel fitting approach which decomposes the extracellularly recorded signal into its presynaptic and postsynaptic components. In prehearing mice, we found signal transmission to be unreliable, with high variability in the transmission delay and in the amplitude of postsynaptic components. These timing and amplitude changes were strongly correlated with the preceding activity. Around hearing onset (P12–P14), the properties of signal transmission converged to the adult-like state which was characterized by high transmission reliability as well as high consistency in timing and amplitude. Although activity-dependent depression was still found in action potentials, EPSP depression no longer played a prominent role. In conclusion, the maturation of synaptic transmission at the calyx of Held seems to be precisely timed to achieve its adult potential by the time acoustically evoked signal processing commences.

The phase of low-frequency sinusoids is encoded in phase-coupled discharges of spherical bushy cells (SBCs) of the anteroventral cochlear nucleus and transmitted to the medial superior olive, where binaural input-coincidence is used for processing of sound source localization. SBCs are innervated by auditory nerve fibers through large, excitatory synapses (endbulbs of Held) and by inhibitory inputs, which effectively reduce SBC discharge rates. Here we monitor presynaptic potentials of endbulb-terminals and postsynaptic spikes of SBCs in extracellular single unit recordings in vivo. We compare postsynaptic phase-coupling of SBCs and their presynaptic immediate auditory nerve input. In all but one SBC discharge rates at the characteristic frequency were reduced pre-to-postsynaptically and phase-coupling accuracy was increased in one-third of them. We investigated the contribution of systemic inhibition on spike timing in SBCs by iontophoretic application of glycine- and GABA-receptor antagonists (strychnine, bicuculline). Discharge rate increased in one-third of the units during antagonist application, which was accompanied by a deterioration of phase-coupling accuracy in half of those units. These results suggest that the phase-coupling accuracy is improved in a subpopulation of SBCs during transmission from the auditory nerve to the SBCs by reduction of spike rates.

Glycine is an inhibitory neurotransmitter activating a chloride conductance in the mammalian CNS. In vitro studies from brain slices revealed a novel presynaptic site of glycine action in the medial nucleus of the trapezoid body (MNTB) which increases the release of the excitatory transmitter glutamate from the calyx of Held. Here, we investigate the action of glycine on action potential firing of single MNTB neurons from the gerbil under acoustic stimulation in vivo. Iontophoretic application of the glycine receptor antagonist strychnine caused a significant decrease in spontaneous and sound-evoked firing rates throughout the neurons' excitatory response areas, with the largest changes at the respective characteristic frequency (CF). The decreased firing rate was accompanied by longer and more variable onset latencies of sound-evoked responses. Outside the neurons' excitatory response areas, firing rates increased during the application of strychnine due to a reduction of inhibitory sidebands, causing a broadening of frequency tuning. These results indicate that glycine enhances the efficacy for on-CF stimuli, while simultaneously suppressing synaptic transmission for off-CF stimuli. These in vivo results provide evidence of multiple excitatory and inhibitory glycine effects on the same neuronal population in the mature mammalian CNS.

The neuronal representation of acoustic amplitude modulations is an important prerequisite for understanding the processing of natural sounds. We investigated this representation in the medial nucleus of the trapezoid body (MNTB) of the Mongolian gerbil using sinusoidal amplitude modulations (SAM). Depending on the SAM's carrier frequency (f(C)) MNTB cells either increase or decrease their discharge rates, indicating underlying excitatory and inhibitory/suppressive mechanisms. As natural sounds typically are composed of multiple spectral components we investigated how stimuli containing two spectral components are represented in the MNTB, especially when they have opposing effects on the discharge rate. Three conditions were compared: SAM stimuli (1) with rate-increasing f(C), (2) with rate-increasing f(C) and an additional unmodulated rate-decreasing pure tone, and (3) with rate-decreasing f(C) and an unmodulated, rate-increasing pure tone. We found that responses under all three conditions showed comparable strength of phase-locking. Adding a rate-decreasing tone to a rate-increasing SAM increased phase-locking for modulation frequencies (f(AM)) of < or = 600 Hz. A comparison of two possible coding strategies--phase-locking vs. envelope reproduction--indicates that both strategies are realized to different degrees depending on the f(AM). We measured latencies for following modulations in rate-increasing and rate-decreasing SAMs using a modified reverse correlation approach. Although latencies varied between 2.5 and 5 ms between cells, a decrease in rate consistently followed an increase in rate with a delay of about 0.2 ms in each cell. These results suggest a temporally precise representation of rate-increasing and rate-decreasing stimuli at the level of the MNTB during dynamic stimulation.

Localization of sounds by the auditory system is based on the analysis of three sources of information: interaural level differences (ILD, caused by an attenuation of the sound as it travels to the more distant ear), interaural time differences (ITD, caused by the additional amount of time it takes for the sound to arrive at the more distant ear), and spectral cues (caused by direction-specific spectral filter properties of the pinnae). Although in a number of psychophysiological studies cortical processes of ITD and ILD analysis were investigated, there is hitherto no evidence on the cortical processing of spectral cues for sound localization. The objective of the present experiment was to test whether it is possible to observe electrophysiological correlates of sound localization based on spectral cues. In an auditory oddball experiment, 80 ms of broadband noise from varying free field locations were presented to inattentive participants. Mismatch negativities (MMNs) were observed for pairs of standards and location deviants located symmetrically with respect to the interaural axis. As interaural time and level differences are identical for such pairs of sounds, the observed MMNs most likely reflect cognitive processes of sound localization utilizing the spectral filter properties of the pinnae. MMN latencies suggest that sound localization based on spectral cues is slower than ITD- or ILD-based localization.

The proteoglycan brevican is a major component of the extracellular matrix of perineuronal nets and is highly enriched in the perisynaptic space suggesting a role for synaptic transmission. We have introduced the calyx of Held in the auditory brainstem as a model system to study the impact of brevican on dynamics and reliability of synaptic transmission. In vivo extracellular single-unit recordings at the calyx of Held in brevican-deficient mice yielded a significant increase in the action potential (AP) transmission delay and a prolongation of pre- and postsynaptic APs. The changes in dynamics of signal transmission were accompanied by the reduction of presynaptic vGlut1 and ultrastructural changes in the perisynaptic space. These data show that brevican is an important mediator of fast synaptic transmission at the calyx of Held.The extracellular matrix is an integral part of the neural tissue. Its most conspicuous manifestation in the brain are the perineuronal nets (PNs) which surround somata and proximal dendrites of distinct neuron types. The chondroitin sulfate proteoglycan brevican is a major component of PNs. In contrast to other PN-comprising proteoglycans (e.g. aggrecan and neurocan), brevican is mainly expressed in the perisynaptic space closely associated with both the pre- and postsynaptic membrane. This specific localization prompted the hypothesis that brevican might play a role in synaptic transmission. In the present study we specifically investigated the role of brevican in synaptic transmission at a central synapse, the calyx of Held in the medial nucleus of the trapezoid body, by the use of in vivo electrophysiology, immunohistochemistry, biochemistry and electron microscopy. In vivo extracellular single-unit recordings were acquired in brevican-deficient mice and the dynamics and reliability of synaptic transmission were compared to wild-type littermates. In knockout mice, the speed of pre-to-postsynaptic action potential (AP) transmission was reduced and the duration of the respective pre- and postsynaptic APs increased. The reliability of signal transmission, however, was not affected by the lack of brevican. The changes in dynamics of signal transmission were accompanied by the reduction of (i) presynaptic vGlut1 and (ii) the size of subsynaptic cavities. The present results suggest an essential role of brevican for the functionality of high-speed synaptic transmission at the calyx of Held.

Frontiers in neural circuits 9, - (2015). doi:10.3389/fncir.2015.00014, Published by Frontiers Research Foundation, Lausanne

We report evidence for a context- and not stimulus-dependent functional asymmetry in the left and right human auditory midbrain, thalamus, and cortex in response to monaural sounds. Neural activity elicited by left- and right-ear stimulation was measured simultaneously in the cochlear nuclei, inferior colliculi (ICs), medial geniculate bodies (MGBs), and auditory cortices (ACs) in 2 functional magnetic resonance imaging experiments. In experiment 1, pulsed noise was presented monaurally to either ear, or binaurally, simulating a moving sound source. In experiment 2, only monaural sounds were presented. The results show a modulation of the neural responses to monaural sounds by the presence of binaural sounds at a time scale of tens of seconds: In the absence of binaural stimulation, the left and right ICs, MGBs, and ACs responded stronger to stimulation of the contralateral ear. When blocks of binaural stimuli were interspersed in the sound sequence, the contralateral preference vanished in those structures in the right hemisphere. The resulting hemispheric asymmetry was similar to the asymmetry demonstrated for spatial sound processing. Taken together, the data demonstrate that functional asymmetries in auditory processing are modulated by context. The observed long time constant suggests that this effect results from a "top-down" mechanism.

The voltage-gated potassium (Kv) channel subunit Kv1.1, encoded by theKcna1gene, is expressed strongly in the ventral cochlear nucleus (VCN) and the medial nucleus of the trapezoid body (MNTB) of the auditory pathway. To examine the contribution of the Kv1.1 subunit to the processing of auditory information,in vivosingle-unit recordings were made from VCN neurons (bushy cells), axonal endings of bushy cells at MNTB cells (calyces of Held), and MNTB neurons ofKcna1-null (-/-) mice and littermate control (+/+) mice. Thresholds and spontaneous firing rates of VCN and MNTB neurons were not different between genotypes. At higher sound intensities, however, evoked firing rates of VCN and MNTB neurons were significantly lower in -/- mice than +/+ mice. The SD of the first-spike latency (jitter) was increased in VCN neurons, calyces, and MNTB neurons of -/- mice compared with +/+ controls. Comparison along the ascending pathway suggests that the increased jitter found in -/- MNTB responses arises mostly in the axons of VCN bushy cells and/or their calyceal terminals rather than in the MNTB neurons themselves. At high rates of sinusoidal amplitude modulations, -/- MNTB neurons maintained high vector strength values but discharged on significantly fewer cycles of the amplitude-modulated stimulus than +/+ MNTB neurons. These results indicate that inKcna1-null mice the absence of the Kv1.1 subunit results in a loss of temporal fidelity (increased jitter) and the failure to follow high-frequency amplitude-modulated sound stimulationin vivo.

Spherical bushy cells (SBCs) of the anteroventral cochlear nucleus (AVCN) receive their main excitatory input from auditory nerve fibers (ANFs) through large synapses, endbulbs of Held. These cells are also the target of inhibitory inputs whose function is not well understood. The present study examines the role of inhibition in the encoding of low-frequency sounds in the gerbil's AVCN. The presynaptic action potentials of endbulb terminals and postsynaptic action potentials of SBCs were monitored simultaneously in extracellular single-unit recordings in vivo. An input-output analysis of presynaptic and postsynaptic activity was performed for both spontaneous and acoustically driven activity. Two-tone stimulation and neuropharmacological experiments allowed the effects of neuronal inhibition and cochlear suppression on SBC activity to be distinguished. Ninety-one percent of SBCs showed significant neuronal inhibition. Inhibitory sidebands enclosed the high- or low-frequency, or both, sides of the excitatory areas of these units; this was reflected as a presynaptic to postsynaptic increase in frequency selectivity of up to one octave. Inhibition also affected the level-dependent responses at the characteristic frequency. Although in all units the presynaptic recordings showed monotonic rate-level functions, this was the case in only half of the postsynaptic recordings. In the other half of SBCs, postsynaptic inhibitory areas overlapped the excitatory areas, resulting in nonmonotonic rate-level functions. The results demonstrate that the sound-evoked spike activity of SBCs reflects the integration of acoustically driven excitatory and inhibitory input. The inhibition specifically affects the processing of the spectral, temporal, and intensity cues of acoustic signals.

The superior paraolivary nucleus (SPN) of the superior olivary complex (SOC) though morphologically well described, has not been characterized physiologically. Here we report the basic response properties of SPN units acquired with extracellular recording techniques under monaural acoustic stimulation in the Mongolian gerbil. Poststimulus-time histograms corresponded to those described earlier for the cat's cochlear nucleus (onset, chopper, primary-like), and partly to those previously acquired in other SOC nuclei (tonic, off/rebound). Two-thirds of the units responded solely to contralateral stimulation (40% excitatory [E], 19% inhibitory [I], 6% mixed [EI]). Most of the remainder responded equally to stimulation from either ear (18% I.I, 9% E.E). Overall, the monaural contralateral input was more effective than the ipsilateral and bilateral input. Characteristic frequencies and response areas covered the entire hearing range of the gerbil and the units mostly showed broad frequency-tuning. In combination, these properties suggest that the SPN might be a constituent of an afferent pathway encoding stimulus features across broad frequency ranges.

GABA and glycine are the major inhibitory transmitters that attune neuronal activity in the CNS of mammals. The respective transmitters are mostly spatially separated, that is, synaptic inhibition in the forebrain areas is mediated by GABA, whereas glycine is predominantly used in the brainstem. Accordingly, inhibition in auditory brainstem circuits is largely mediated by glycine, but there are few auditory synapses using both transmitters in maturity. Little is known about physiological advantages of such a two-transmitter inhibitory mechanism. We explored the benefit of engaging both glycine and GABA with inhibition at the endbulb of Held-spherical bushy cell synapse in the auditory brainstem of juvenile Mongolian gerbils. This model synapse enables selectivein vivoactivation of excitatory and inhibitory neuronal inputs through systemic sound stimulation and precise analysis of the input (endbulb of Held) output (spherical bushy cell) function. The combination ofin vivoand slice electrophysiology revealed that the dynamic AP inhibition in spherical bushy cells closely matches the inhibitory conductance profile determined by the glycine-R and GABAA-R. The slow and potent glycinergic component dominates the inhibitory conductance, thereby primarily accounting for its high-pass filter properties. GABAergic transmission enhances the inhibitory strength and shapes its duration in an activity-dependent manner, thus increasing the inhibitory potency to suppress the excitation through the endbulb of Held. Finally,in silicomodeling provides a strong link betweenin vivoand slice data by simulating the interactions between the endbulb- and the synergistic glycine-GABA-conductances duringin vivo-like spontaneous and sound evoked activities.

Localization accuracy and acuity for low- (0.375-0.75 kHz; LN) and high-frequency (2.25-4.5 kHz; HN) noise bands were examined in young (20-29 years) and older adults (65-83 years) in the acoustic free-field. A pointing task was applied to quantify accuracy, while acuity was inferred from minimum audible angle (MAA) thresholds measured with an adaptive 3-alternative forced-choice procedure. Accuracy decreased with laterality and age. From young to older adults, the accuracy declined by up to 23 % for the low-frequency noise band across all lateralities. The mean age effect was even more pronounced on MAA thresholds. Thus, age was a strong predictor for MAA thresholds for both LN and HN bands. There was no significant correlation between hearing status and localization performance. These results suggest that central auditory processing of space declines with age and is mainly driven by age-related changes in the processing of binaural cues (interaural time difference and interaural intensity difference) and not directly induced by peripheral hearing loss. We conclude that the representation of the location of sound sources becomes blurred with age as a consequence of declined temporal processing, the effect of which becomes particularly evident for MAA thresholds, where two closely adjoining sound sources have to be separated. While localization accuracy and MAA were not correlated in older adults, only a weak correlation was found in young adults. These results point to an employment of different processing strategies for localization accuracy and acuity.

The spatial distribution of neurons with different binaural response properties was studied in two isofrequency areas of the inferior colliculus (IC) of the gerbil ( Meriones unguiculatus ). Single units were recorded in dorsomedial-to-ventrolaterally oriented electrode penetrations at different rostrocaudal positions, within a low (1–2 kHz; N = 108) and a high (23–27 kHz; N = 90) ‘iso-frequency’ sheet. Response types were not equally represented within the two layers. Within low-frequency regions, 41% of the units were excited following sound stimulation of either ear (EE), 21% received an excitatory input from one and an inhibitory input from the other ear (EI), and 12% were monaural (E0), while within high-frequency regions the distribution was 20% EE, 47% EI and 18% E0. However, the spatial arrangement of EE, EI and E0, within the dorsomedial-to-ventrolateral extent of the isofrequency sheets, was on the whole comparable within the two regions: EE-units were accumulated dorsomedially and EI-units ventrolaterally in the respective isofrequency sheets. E0-units were distributed equally within the low-frequency sheet but occurred more frequently in the middle part of the high-frequency lamina. About equal proportions of the units (low frequencies 9%; high frequencies 7%) had complex binaural response characteristics and were characterized as E/IE. In the rostrocaudal dimension of the nucleus, orderly arrangement of different unit types was less obvious. The results show that there is a tendency for grouping of different binaural unit types within the inferior colliculus. However, these unit types are not strictly segregated. Furthermore, it was shown that, despite the differences found in low- and high-frequency sites, there is a common scheme of ‘binaural representation’ across frequencies within the IC. Provided that EE-, EI-, and monaural response characteristics originate from separate sources, the data point to a convergence of binaural brainstem afferents within the IC.

Difference in the processing of motion and static sounds in the human cortex was studied by electroencephalography with subjects performing an active discrimination task. Sound bursts were presented in the acoustic free-field between 47° to the left and 47° to the right under three different stimulus conditions: (i) static, (ii) leftward motion, and (iii) rightward motion. In an active oddball design, subject was asked to detect target stimuli which were randomly embedded within a stream of frequently occurring non-target events (i.e. ‘standards’) and rare non-target stimuli (i.e. ‘deviants’). The respective acoustic stimuli were presented in blocks with each stimulus type presented in either of three stimulus conditions: as target, as non-target, or as standard. The analysis focussed on the event related potentials evoked by the different stimulus types under the respective standard condition. Same as in previous studies, all three different acoustic stimuli elicited the obligatory P1/N1/P2 complex in the range of 50-200 ms. However, comparisons of ERPs elicited by static stimuli and both kinds of motion stimuli yielded differences as early as ∼100 ms after stimulus-onset, i.e. at the level of the exogenous N1 and P2 components. Differences in signal amplitudes were also found in a time window 300-400 ms (‘ d 300-400 ms’ component in ‘ motion -minus- static ’ difference wave). For motion stimuli, the N1 amplitudes were larger over the hemisphere contralateral to the origin of motion, while for static stimuli N1 amplitudes over both hemispheres were in the same range. Contrary to the N1 component, the ERP in the ‘ d 300-400 ms’ time period showed stronger responses over the hemisphere contralateral to motion termination, with the static stimuli again yielding equal bilateral amplitudes. For the P2 component a motion-specific effect with larger signal amplitudes over the left hemisphere was found compared to static stimuli. The presently documented N1 components comply with the results of previous studies on auditory space processing and suggest a contralateral dominance during the process of cortical integration of spatial acoustic information. Additionally, the cortical activity in the ‘d300-400 ms’ time period indicates, that in addition to the motion origin (as reflected by the N1) also the direction of motion (leftward/ rightward motion) or rather motion termination is cortically encoded. These electrophysiological results are in accordance with the ‘snap shot’ hypothesis, assuming that auditory motion processing is not based on a genuine motion-sensitive system, but rather on a comparison process of spatial positions of motion origin (onset) and motion termination (offset). Still, specificities of the present P2 component provides evidence for additional motion-specific processes possibly associated with the evaluation of motion-specific attributes, i.e. motion direction and/or velocity which is preponderant in the left hemisphere.

The present study investigated the development of two parameters of spatial acoustic perception in children and adolescents with normal hearing, aged 6–18 years. Auditory localization accuracy was quantified by means of a sound source identification task and auditory spatial discrimination acuity by measuring minimum audible angles (MAA). Both low- and high-frequency noise bursts were employed in the tests, thereby separately addressing auditory processing based on interaural time and intensity differences. Setup consisted of 47 loudspeakers mounted in the frontal azimuthal hemifield, ranging from 90° left to 90° right (–90°, +90°). Target signals were presented from 8 loudspeaker positions in the left and right hemifields (±4°, ±30°, ±60° and ±90°). Localization accuracy and spatial discrimination acuity showed different developmental courses. Localization accuracy remained stable from the age of 6 onwards. In contrast, MAA thresholds and interindividual variability of spatial discrimination decreased significantly with increasing age. Across all age groups, localization was most accurate and MAA thresholds were lower for frontal than for lateral sound sources, and for low-frequency compared to high-frequency noise bursts. The study also shows better performance in spatial hearing based on interaural time differences rather than on intensity differences throughout development. These findings confirm that specific aspects of central auditory processing show continuous development during childhood up to adolescence.

Auditory extinction and spatio-temporal order judgment (STOJ) were assessed in patients with acquired brain damage by systematically manipulating onset times in bilateral stimulation under free-field conditions. We tested the hypothesis that extinction will be reduced by increasing stimulus onset asynchrony. Two groups of patients with right-hemisphere (RH, n=17) or left-hemisphere (LH, n=17) damage were investigated in comparison to a healthy control group (n=12). The patients were recruited based on previously diagnosed impairments: auditory discrimination deficits with (RH(E)/LH(E)) or without extinction (RH(0)/LH(0)) due to cortical and/or subcortical temporo-parietally centred lesions. Stimuli were presented bilaterally in the acoustic free-field, with an onset asynchrony of ± 30 to ± 150 ms, or unilaterally, from speakers located ± 60°. Low frequency (LF) and high frequency (HF) stimuli were used to address spatial auditory processing in the horizontal plane based on the two main cues of interaural time and interaural intensity differences, respectively. The subjects' task was to indicate whether they perceived one (left or right) or two stimuli (left and right), and in the case of two make an STOJ (left or right first). Temporal asynchrony significantly reduced extinction in those patients that previously exhibited extinction for bilateral-simultaneous stimulation (RH(E)/LH(E)). In addition, their error rates in STOJ were higher than the controls'. A number of patients with no previous signs of extinction in bilateral-simultaneous stimulation (RH(0)/LH(0)) also showed impaired STOJ: in RH(0) patients this was specific to ipsilesional-leading stimuli, whilst in LH(0) patients no side-specific effect was observed. The data support the notion of differential roles for the two hemispheres in spatio-temporal auditory perception and are discussed with respect to prevalent models of extinction and its possible long-term reduction.

Voltage-gated potassium (Kv) channels containing Kv1.1 subunits are strongly expressed in neurons that fire temporally precise action potentials (APs). In the auditory system, AP timing is used to localize sound sources by integrating interaural differences in time (ITD) and intensity (IID) using sound arriving at both cochleae. In mammals, the first nucleus to encode IIDs is the lateral superior olive (LSO), which integrates excitation from the ipsilateral ventral cochlear nucleus and contralateral inhibition mediated via the medial nucleus of the trapezoid body. Previously we reported that neurons in this pathway show reduced firing rates, longer latencies and increased jitter in Kv1.1 knockout (Kcna1−/−) mice. Here, we investigate whether these differences have direct impact on IID processing by LSO neurons. Single-unit recordings were made from LSO neurons of wild-type (Kcna1+/+) and from Kcna1−/− mice. IID functions were measured to evaluate genotype-specific changes in integrating excitatory and inhibitory inputs. In Kcna1+/+ mice, IID sensitivity ranged from +27 dB (excitatory ear more intense) to −20 dB (inhibitory ear more intense), thus covering the physiologically relevant range of IIDs. However, the distribution of IID functions in Kcna1−/− mice was skewed towards positive IIDs, favouring ipsilateral sound positions. Our computational model revealed that the reduced performance of IID encoding in the LSO of Kcna1−/− mice is mainly caused by a decrease in temporal fidelity along the inhibitory pathway. These results imply a fundamental role for Kv1.1 in temporal integration of excitation and inhibition during sound source localization.

To investigate the influence of spatial information in auditory scene analysis, polyphonic music (three parts in different timbres) was composed and presented in free field. Each part contained large falling interval jumps in the melody and the task of subjects was to detect these events in one part ("target part") while ignoring the other parts. All parts were either presented from the same location (0 degrees; overlap condition) or from different locations (-28 degrees, 0 degrees, and 28 degrees or -56 degrees, 0 degrees, and 56 degrees in the azimuthal plane), with the target part being presented either at 0 degrees or at one of the right-sided locations. Results showed that spatial separation of 28 degrees was sufficient for a significant improvement in target detection (i.e., in the detection of large interval jumps) compared to the overlap condition, irrespective of the position (frontal or right) of the target part. A larger spatial separation of the parts resulted in further improvements only if the target part was lateralized. These data support the notion of improvement in the suppression of interfering signals with spatial sound source separation. Additionally, the data show that the position of the relevant sound source influences auditory performance.

In the auditory forebrain (field L) of the European starling (Sturnus culgaris), single unit responses were recorded for a wide range of complex stimuli, comprising different forms of amplitude and frequency modulation. About two-third of the units locked to sinusoidal modulation regardless of whether frequency (SFM) or amplitude (SAM) was modulated. On average, however, frequency led to stronger synchronization. Both the proportion of phase locking and its mean strength showed a low-pass dependence on modulation frequency. The lower efficiency of amplitude modulation is also visible in unit responses when SAM is combined with (random) frequency modulation. For the assessment of response strength and its comparison across the tested repertoire of complex stimuli, a new index (REX) is introduced which primarily weighs similarity of the spike trains in identically repeated stimulus runs. Applied to a set of 311 field L neurons, also this approach discloses the two stimulus classes lacking frequency modulation (pure tone and SAM) as the least effective. A new measure for response latency, the Effective Response Delay (ERD), based on the spike-triggered analysis of responses to randomly frequency-modulated sounds (RFM), reflects physiological delays better than conventional latency. So, ERD correction of SAM and SFM Period Histograms allowed to disclose response effective stimulus ranges independent of modulation frequency.

The calyx of Held synapse in the medial nucleus of the trapezoid body of the auditory brainstem has become an establishedin vitromodel to study the development of fast glutamatergic transmission in the mammalian brain. However, we still lackin vivodata at this synapse on the maturation of spontaneous and sound-evoked discharge activity before and during the early phase of acoustically evoked signal processing (i.e., before and after hearing onset). Here we reportin vivosingle-unit recordings in mice from postnatal day 8 (P8) to P28 with a specific focus on developmental changes around hearing onset (P12). Data were obtained from two mouse strains commonly used in brain slice recordings: CBA/J and C57BL/6J. Spontaneous discharge rates progressively increased from P8 to P13, initially showing bursting patterns and large coefficients of variation (CVs), which changed to more continuous and random discharge activity accompanied by gradual decrease of CV around hearing onset. From P12 on, sound-evoked activity yielded phasic-tonic discharge patterns with discharge rates increasing up to P28. Response thresholds and shapes of tuning curves were adult-like by P14. A gradual shortening in response latencies was observed up to P18. The three-dimensional tonotopic organization of the medial nucleus of the trapezoid body yielded a high-to-low frequency gradient along the mediolateral and dorsoventral but not in the rostrocaudal axes. These data emphasize that models of signal transmission at the calyx of Held based onin vitrodata have to take developmental changes in firing rates and response latencies up to the fourth postnatal week into account.

Transmission at central synapses exhibits rapid changes in response amplitude under different patterns of stimulation. Whether the delay associated with the transmission of action potentials is similarly modifiable is important for temporally precise computations. We address this question at the calyx of Held of the medial nucleus of the trapezoid body (MNTB) in Mongolian gerbils in vivo using extracellular recordings. Here the pre- and postsynaptic activity can be observed simultaneously, allowing the definition of an action potential transmission delay (ATD) from the pre- to the postsynaptic side. We find the ATD to increase as a function of spike rate (10-40%). The temporal dynamics of the ATD increase exhibit an exponential shape with activity-dependent time constants ( approximately 15-25 ms). Recovery dynamics of ATD were mono- (20-70 ms) or biexponential with fast (3-20 ms) and slow time constants (50-500 ms). Using a phenomenological model to capture ATD dynamics, we estimated DeltaATD = 5-30 micros per transmitted action potential. Using vocalizations and cage noise stimuli, we confirm that substantial changes in ATD occur in natural situations. Because the ATD changes cover the behaviorally relevant range of interaural time differences in gerbils, these results could provide constraints for models of sound localization.

Background Lateralized processing of speech is a well studied phenomenon in humans. Both anatomical and neurophysiological studies support the view that nonhuman primates and other animal species also reveal hemispheric differences in areas involved in sound processing. In recent years, an increasing number of studies on a range of taxa have employed an orienting paradigm to investigate lateralized acoustic processing. In this paradigm, sounds are played directly from behind and the direction of turn is recorded. This assay rests on the assumption that a hemispheric asymmetry in processing is coupled to an orienting bias towards the contralateral side. To examine this largely untested assumption, speech stimuli as well as artificial sounds were presented to 224 right-handed human subjects shopping in supermarkets in Germany and in the UK. To verify the lateralized processing of the speech stimuli, we additionally assessed the brain activation in response to presentation of the different stimuli using functional magnetic resonance imaging (fMRI). Results In the naturalistic behavioural experiments, there was no difference in orienting behaviour in relation to the stimulus material (speech, artificial sounds). Contrary to our predictions, subjects revealed a significant left bias, irrespective of the sound category. This left bias was slightly but not significantly stronger in German subjects. The fMRI experiments confirmed that the speech stimuli evoked a significant left lateralized activation in BA44 compared to the artificial sounds. Conclusion These findings suggest that in adult humans, orienting biases are not necessarily coupled with lateralized processing of acoustic stimuli. Our results – as well as the inconsistent orienting biases found in different animal species – suggest that the orienting assay should be used with caution. Apparently, attention biases, experience, and experimental conditions may all affect head turning responses. Because of the complexity of the interaction of factors, the use of the orienting assay to determine lateralized processing of sound stimuli is discouraged.

The present study reports the hemispheric specificity of spatial auditory processing in 15 healthy subjects by measuring location mismatch negativity (MMN) under free field stimulation. The aim was to decide between the partly inconsistent hypotheses of contralateral and/or right-hemispheric dominance in spatial processing in the auditory cortex. The laterality of deviant-standard positions were systematically varied covering the whole of the frontal hemifield from 90 degrees left to 90 degrees right, while the spatial separation of deviant and standard were fixed at 17 degrees. This enabled the evaluation of the specific location-MMNs relating to distinct cortical processing of acoustic space. The inter-hemispheric comparison of the amplitudes of MMNs showed that spatial deviation towards the periphery at -/+17 degrees (relative to 0 degrees -standard) and at -/+90 degrees (relative to -/+73 degrees -standard) elicited a salient contralateral activation. In contrast, positional changes towards front at -/+56 degrees -positions (relative to -/+73 degrees -standard) resulted equal bilateral MMNs. Further, MMN latencies became longer with increasing laterality of respective deviant-standard pairs. Thus, the present study suggests a contralateral pre-attentive cortical processing of acoustic space information in the free field. The direction of positional changes ('towards periphery' vs. 'towards front') seems to augment or reduce this contralateral effect. The sound source discrimination performance across space is mirrored by the location-MMN latency.

The medial nucleus of the trapezoid body (MNTB) is a distinct nucleus in the superior olivary complex that transforms excitatory input from the cochlear nucleus into a widespread inhibitory output to distinct auditory brainstem nuclei. Few studies have dealt with the response properties of MNTB neurons to sound stimulation using in vivo preparations. In order to have a better understanding of the functional significance of the MNTB in auditory processing we report the basic temporal and spectral response properties of its principal cells using single-unit extracellular recordings to acoustic stimulation with pure tones and amplitude-modulated stimuli in the rat. Ninety-seven per cent of units showed V-shaped frequency response areas. Rate level functions were mainly saturating (51%) or monotonic (45%) at high intensities. Post-stimulus time histograms typically were characterised as primary-like with notch (59%) or primary-like (33%). Units showed good phase-locking to sinusoidally amplitude-modulated signals with vector strength VS values up to 0.87. Modulation transfer functions had low-pass shapes at near-threshold levels, with cut-off frequencies ranging from 370 to 1270 Hz. Exploration of the relationship between the temporal and spectral properties and the location of the units in the MNTB yielded characteristic frequency (CF)-dependent response properties (latency, Q 10 and cut-off frequency) following a medio-lateral gradient, and CF-independent response features (maximum firing rate) following a dorso-ventral gradient.

Recent studies utilizing the mismatch negativity (MMN) event-related potential (ERP) revealed that when a repetitive sequence of sinusoidal tones is presented, the occasional insertion of a short deviation into some of the tones leads to the elicitation of an MMN only if it occurs during the initial 300 ms, but not beyond. In contrast, deviations occurring in speech sounds elicit MMN even beyond 300 ms. We conducted two experiments to resolve this conflict. We hypothesised that an additional transient within an otherwise unstructured tone may overcome this limitation. First, we tested for MMN to a deviance at the terminal part of a 650 ms tone which did or did not contain a gap. Only when the tone included the gap, MMN was obtained. Second, we compared the gap condition with two noise conditions, in which the gap was replaced by modulated white noise. The noise conditions differed with respect to the saliency of the perceived interruption of the tone. In all three conditions, MMN was elicited. These results demonstrate that structuring a sinusoidal tone by a gap or a noise interval is sufficient to regain MMN. It is suggested that the introduction of an additional transient triggers a new integration window overcoming the temporal constraints of automatic tone representation. This resolves the seeming contradiction between MMN studies using tonal and speech sounds.

We use novel noise-like sound stimuli to identify cortical areas in which the functional magnetic resonance signal covaries with spectral and temporal acoustic complexity. The results support a model of hemispheric functional asymmetry for fine-grained spectral and fast temporal processing.

The present study investigates the acoustic basis of the hemispheric asymmetry for the processing of speech and music. Experiments on this question ideally involve stimuli that are perceptually unrelated to speech and music, but contain acoustic characteristics of both. Stimuli in previous studies were derived from speech samples or tonal sequences. Here we introduce a new class of noise-like sound stimuli with no resemblance of speech or music that permit independent parametric variation of spectral and temporal acoustic complexity. Using these stimuli in a functional MRI experiment, we test the hypothesis of a hemispheric asymmetry for the processing of spectral and temporal sound structure by seeking cortical areas in which the blood oxygen level dependent (BOLD) signal covaries with the number of simultaneous spectral components (spectral complexity) or the temporal modulation rate (temporal complexity) of the stimuli. BOLD-responses from the left and right Heschl's gyrus (HG) and part of the right superior temporal gyrus covaried with the spectral parameter, whereas covariation analysis for the temporal parameter highlighted an area on the left superior temporal gyrus. The portion of superior temporal gyrus in which asymmetrical responses are apparent corresponds to the antero-lateral auditory belt cortex, which has been implicated with spectral integration in animal studies. Our results support a similar function of the anterior auditory belt in humans. The findings indicate that asymmetrical processing of complex sounds in the cerebral hemispheres does not depend on semantic, but rather on acoustic stimulus characteristics.

Horizontal sound localization relies on the extraction of binaural acoustic cues by integration of the signals from the two ears at the level of the brainstem. The present experiment was aimed at detecting the sites of binaural integration in the human brainstem using functional magnetic resonance imaging and a binaural difference paradigm, in which the responses to binaural sounds were compared with the sum of the responses to the corresponding monaural sounds. The experiment also included a moving sound condition, which was contrasted against a spectrally and energetically matched stationary sound condition to assess which of the structures that are involved in general binaural processing are specifically specialized in motion processing. The binaural difference contrast revealed a substantial binaural response suppression in the inferior colliculus in the midbrain, the medial geniculate body in the thalamus and the primary auditory cortex. The effect appears to reflect an actual reduction of the underlying activity, probably brought about by binaural inhibition or refractoriness at the level of the superior olivary complex. Whereas all structures up to and including the primary auditory cortex were activated as strongly by the stationary as by the moving sounds, non-primary auditory fields in the planum temporale responded selectively to the moving sounds. These results suggest a hierarchical organization of auditory spatial processing in which the general analysis of binaural information begins as early as the brainstem, while the representation of dynamic binaural cues relies on non-primary auditory fields in the planum temporale.

Responses of anteroventral cochlear nucleus (AVCN) neurons in developing gerbils were obtained to single-tone stimuli, and two-tone stimuli elicited by best frequency probes presented over a range of intensities. Neurons displayed Type I, Type I/III, and Type III receptive field patterns. Best frequencies ranged from 1.5 to 10.0 kHz. Two-tone suppression (2TS) was first observed in 5 of 16 neurons examined at 14 dab, and in all neurons examined in gerbils aged 15 to 60 dab. Suppression areas grew larger, and discharge rate reductions became greater with age. Features of the two-tone responses that were highly correlated with single-tone responses across age groups include maximum rate reductions and suppression area thresholds. The intensity level of the CF probe-tone also influenced these features of 2TS. Maximum rate reductions to below spontaneous rate levels of activity were common across age groups. Results suggest that the cochlear amplifier is present and fundamentally adult-like by 15 dab for the regions of the cochlea coding the mid frequencies in gerbil. Over the subsequent week, contributions to the developing two-tone responses by the cochlear amplifier increase slightly. Two-tone responses are influenced by central inhibitory mechanisms as early as 14 dab.

This report describes the postnatal development of hearing range, auditory sensitivity and tonotopy within the inferior colliculus (IC) of a mammal specialized for ultrasonic hearing. The experimental animal, Carollia perspicillata, has an adult hearing range of 7-110 kHz (characteristic frequencies) but lack any significant overrepresentation of a limited frequency band as known for rhinolophoid bats and Pteronotus. The audiogram of the newborn Carollia includes characteristic frequencies from 8 to 76 kHz, which is about 65% of the adult hearing range. As in adults, low frequencies are represented in the dorsolateral portion of the IC. However, at birth the ventromedial IC is non-responsive to acoustic stimulation up to intensities of 90 dB SPL. During development there is a progressive conversion of non-responsive IC areas into acoustically responsive slabs with characteristic frequencies above 76 kHz along the dorsolateral to ventromedial (low-to-high frequency) IC axis. This development is superimposed by a non-uniform shift of characteristic frequency: a decrease of CFs in dorsolateral regions, and an increase of CFs in ventromedial areas. The results suggest a bidirectional shift of frequency representation along the cochlear tonotopic axis.

The response characteristic of auditory forebrain neurons in the European starling was established both with artificial stimuli (AS) and a conspecific territorial song as a natural stimulus (NS1). Applying experimenter-centred statistical methods for response detection and for scaling response strength, and spike-triggered analyses for the delimitation of the key sound parameters (spectrotemporal receptive field STRF, Aertsen et al. 1980) the study aimed at disclosing differences in the processing of the two stimulus classes, AS and NS. With the STRF as reference, we find congruence (1) in the best frequency with those determined under sweep and bandpass noise stimulation, (2) in response latency, and (3) in response-intensity dependence, further similarity in the overall frequency characteristic. Partitioning the song into 42 acoustically defined segments allowed to further delimit the response criteria under natural stimulation. They are easily understood from the AS response characteristics: (1) In the neuronal sample as a whole, long segments are more effective than short and, among the short, loud segments are more effective than faint; (2) Units showing their best excitatory response to AS in a certain frequency band are most probably excited by segments with a high proportion of their power concentrated upon or near this band; (3) Units with a slow (build-up) AS response react to a lower number of song segments than those dynamically following AS transients. Our data give no hint towards adaptive, feature detection properties of single neurons in field L. Instead, these neurons appear to base their response solely on the short-time spectrotemporal structure of the stimulus, irrespective of its natural or artificial origin.

Background: The giant synapses of Held play an important role in high-fidelity auditory processing and provide a model system for synaptic transmission at central synapses. Whether transmission of action potentials can fail at these synapses has been investigated in recent studies. At the endbulbs of Held in the anteroventral cochlear nucleus (AVCN) a consistent picture emerged, whereas at the calyx of Held in the medial nucleus of the trapezoid body (MNTB) results on the reliability of transmission remain inconsistent. In vivo this discrepancy could be due to the difficulty in identifying failures of transmission. Methods/Findings: We introduce a novel method for detecting unreliable transmission in vivo. Based on the temporal relationship between a cells’ waveform and other potentials in the recordings, a statistical test is developed that provides a balanced decision between the presence and the absence of failures. Its performance is quantified using simulated voltage recordings and found to exhibit a high level of accuracy. The method was applied to extracellular recordings from the synapses of Held in vivo. At the calyces of Held failures of transmission were found only rarely. By contrast, at the endbulbs of Held in the AVCN failures were found under spontaneous, excited, and suppressed conditions. In accordance with previous studies, failures occurred most abundantly in the suppressed condition, suggesting a role for inhibition. Conclusions/Significance: Under the investigated activity conditions/anesthesia, transmission seems to remain largely unimpeded in the MNTB, whereas in the AVCN the occurrence of failures is related to inhibition and could be the basis/ result of computational mechanisms for temporal processing. More generally, our approach provides a formal tool for studying the reliability of transmission with high statistical accuracy under typical in vivo recording conditions.

The postnatal development of midbrain tonotopy was investigated in the inferior colliculus (IC) of the south Indian CF-FM bat Hipposideros speoris. The developmental progress of the three-dimensional frequency representation was determined by systematic stereotaxic recordings of multiunit clusters from the 1st up to the 7th postnatal week. Additional developmental measures included the tuning characteristics of single units (Figs. 3f; 4f; 5f), the analysis of the vocalised pulse repertoire (Figs. 3e, 4e, 5e), and morphometric reconstructions of the brains of all experimental animals (Fig. 1). The maturation of auditory processing could be divided into two distinct, possibly overlapping developmental periods: First, up to the 5th week, the orderly tonotopy in the IC developed, beginning with the low frequency representation and progressively adding the high frequency representation. With regard to the topology of isofrequency sheets within the IC, maturation progresses from dorsolateral to ventromedial (Figs. 3c, 4c). At the end of this phase the entire IC becomes specialised for narrowly tuned and sensitive frequency processing. This includes the establishment of the 'auditory fovea', i.e. the extensive spatial representation of a narrow band of behaviorally relevant frequencies in the ventromedial part of the IC. In the 5th postnatal week the auditory fovea is concerned with frequencies from 100-118 kHz (Fig. 4c, d). During subsequent development, the frequency tuning of the auditory fovea increases by 20-25 kHz and finally attains the adult range of ca. 125-140 kHz. During this process, neither the bandwidth of the auditory fovea (15-20 kHz) nor the absolute sensitivity of its units (ca. 50 dB SPL) were changed. Further maturation occurred at the single unit level: the sharpness of frequency tuning increased from the 5th to the 7th postnatal weeks (Q-10-dB-values up to 30-60), and upper thresholds emerged (Figs. 4f, 5f). Although in the adult the frequency of the auditory fovea matches that of the vocalised pulses, none of the juvenile bats tested from the 5th to the 7th weeks showed such a frequency match between vocalisation and audition (Figs. 4e, 5e). The results show that postnatal maturation of audition in hipposiderid bats cannot be described by a model based on a single developmental parameter.