Highly branched and complementary distributions of layer 5 and layer 6 auditory corticofugal axons in mouse.

The auditory cortex exerts a powerful, yet heterogeneous, effect on subcortical targets. Auditory corticofugal projections emanate from layers 5 and 6 and have complementary physiological properties. While several studies suggested that layer 5 corticofugal projections branch widely, others suggested that multiple independent projections exist. Less is known about layer 6; no studies have examined whether the various layer 6 corticofugal projections are independent. Therefore, we examined branching patterns of layers 5 and 6 auditory corticofugal neurons, using the corticocollicular system as an index, using traditional and novel approaches. We confirmed that dual retrograde injections into the mouse inferior colliculus and auditory thalamus co-labeled subpopulations of layers 5 and 6 auditory cortex neurons. We then used an intersectional approach to relabel layer 5 or 6 corticocollicular somata and found that both layers sent extensive branches to multiple subcortical structures. Using a novel approach to separately label layers 5 and 6 axons in individual mice, we found that layers 5 and 6 terminal distributions partially spatially overlapped and that giant terminals were only found in layer 5-derived axons. Overall, the high degree of branching and complementarity in layers 5 and 6 axonal distributions suggest that corticofugal projections should be considered as 2 widespread systems, rather than collections of individual projections.

Incorporating models of subcortical processing improves the ability to predict EEG responses to natural speech.

The goal of describing how the human brain responds to complex acoustic stimuli has driven auditory neuroscience research for decades. Often, a systems-based approach has been taken, in which neurophysiological responses are modeled based on features of the presented stimulus. This includes a wealth of work modeling electroencephalogram (EEG) responses to complex acoustic stimuli such as speech. Examples of the acoustic features used in such modeling include the amplitude envelope and spectrogram of speech. These models implicitly assume a direct mapping from stimulus representation to cortical activity. However, in reality, the representation of sound is transformed as it passes through early stages of the auditory pathway, such that inputs to the cortex are fundamentally different from the raw audio signal that was presented. Thus, it could be valuable to account for the transformations taking place in lower-order auditory areas, such as the auditory nerve, cochlear nucleus, and inferior colliculus (IC) when predicting cortical responses to complex sounds. Specifically, because IC responses are more similar to cortical inputs than acoustic features derived directly from the audio signal, we hypothesized that linear mappings (temporal response functions; TRFs) fit to the outputs of an IC model would better predict EEG responses to speech stimuli. To this end, we modeled responses to the acoustic stimuli as they passed through the auditory nerve, cochlear nucleus, and inferior colliculus before fitting a TRF to the output of the modeled IC responses. Results showed that using model-IC responses in traditional systems analyzes resulted in better predictions of EEG activity than using the envelope or spectrogram of a speech stimulus. Further, it was revealed that model-IC derived TRFs predict different aspects of the EEG than acoustic-feature TRFs, and combining both types of TRF models provides a more accurate prediction of the EEG response.

Corticofugal regulation of predictive coding.

Sensory systems must account for both contextual factors and prior experience to adaptively engage with the dynamic external environment. In the central auditory system, neurons modulate their responses to sounds based on statistical context. These response modulations can be understood through a hierarchical predictive coding lens: responses to repeated stimuli are progressively decreased, in a process known as repetition suppression, whereas unexpected stimuli produce a prediction error signal. Prediction error incrementally increases along the auditory hierarchy from the inferior colliculus (IC) to the auditory cortex (AC), suggesting that these regions may engage in hierarchical predictive coding. A potential substrate for top-down predictive cues is the massive set of descending projections from the AC to subcortical structures, although the role of this system in predictive processing has never been directly assessed. We tested the effect of optogenetic inactivation of the auditory cortico-collicular feedback in awake mice on responses of IC neurons to stimuli designed to test prediction error and repetition suppression. Inactivation of the cortico-collicular pathway led to a decrease in prediction error in IC. Repetition suppression was unaffected by cortico-collicular inactivation, suggesting that this metric may reflect fatigue of bottom-up sensory inputs rather than predictive processing. We also discovered populations of IC units that exhibit repetition enhancement, a sequential increase in firing with stimulus repetition. Cortico-collicular inactivation led to a decrease in repetition enhancement in the central nucleus of IC, suggesting that it is a top-down phenomenon. Negative prediction error, a stronger response to a tone in a predictable rather than unpredictable sequence, was suppressed in shell IC units during cortico-collicular inactivation. These changes in predictive coding metrics arose from bidirectional modulations in the response to the standard and deviant contexts, such that the units in IC responded more similarly to each context in the absence of cortical input. We also investigated how these metrics compare between the anesthetized and awake states by recording from the same units under both conditions. We found that metrics of predictive coding and deviance detection differ depending on the anesthetic state of the animal, with negative prediction error emerging in the central IC and repetition enhancement and prediction error being more prevalent in the absence of anesthesia. Overall, our results demonstrate that the AC provides cues about the statistical context of sound to subcortical brain regions via direct feedback, regulating processing of both prediction and repetition.

Midbrain-Level Neural Correlates of Behavioral Tone-in-Noise Detection: Dependence on Energy and Envelope Cues.

Hearing in noise is a problem often assumed to depend on encoding of energy level by channels tuned to target frequencies, but few studies have tested this hypothesis. The present study examined neural correlates of behavioral tone-in-noise (TIN) detection in budgerigars (Melopsittacus undulatus, either sex), a parakeet species with human-like behavioral sensitivity to many simple and complex sounds. Behavioral sensitivity to tones in band-limited noise was assessed using operant-conditioning procedures. Neural recordings were made in awake animals from midbrain-level neurons in the inferior colliculus, the first processing stage of the ascending auditory pathway with pronounced rate-based encoding of stimulus amplitude modulation. Budgerigar TIN detection thresholds were similar to human thresholds across the full range of frequencies (0.5-4 kHz) and noise levels (45-85 dB SPL) tested. Also as in humans, thresholds were minimally affected by a challenging roving-level condition with random variation in background-noise level. Many midbrain neurons showed a decreasing response rate as TIN signal-to-noise ratio (SNR) was increased by elevating the tone level, a pattern attributable to amplitude-modulation tuning in these cells and the fact that higher SNR tone-plus-noise stimuli have flatter amplitude envelopes. TIN thresholds of individual neurons were as sensitive as behavioral thresholds under most conditions, perhaps surprisingly even when the unit's characteristic frequency was tuned an octave or more away from the test frequency. A model that combined responses of two cell types enhanced TIN sensitivity in the roving-level condition. These results highlight the importance of midbrain-level envelope encoding and off-frequency neural channels for hearing in noise.SIGNIFICANCE STATEMENT Detection of target sounds in noise is often assumed to depend on energy-level encoding by neural processing channels tuned to the target frequency. In contrast, we found that tone-in-noise sensitivity in budgerigars was often greatest in midbrain neurons not tuned to the test frequency, underscoring the potential importance of off-frequency channels for perception. Furthermore, the results highlight the importance of envelope processing for hearing in noise, especially under challenging conditions with random variation in background noise level over time.

Modulation of the Primary Auditory Thalamus When Recognizing Speech with Background Noise.

Recognizing speech in background noise is a strenuous daily activity, yet most humans can master it. An explanation of how the human brain deals with such sensory uncertainty during speech recognition is to-date missing. Previous work has shown that recognition of speech without background noise involves modulation of the auditory thalamus (medial geniculate body; MGB): there are higher responses in left MGB for speech recognition tasks that require tracking of fast-varying stimulus properties in contrast to relatively constant stimulus properties (e.g., speaker identity tasks) despite the same stimulus input. Here, we tested the hypotheses that (1) this task-dependent modulation for speech recognition increases in parallel with the sensory uncertainty in the speech signal, i.e., the amount of background noise; and that (2) this increase is present in the ventral MGB, which corresponds to the primary sensory part of the auditory thalamus. In accordance with our hypothesis, we show, by using ultra-high-resolution functional magnetic resonance imaging (fMRI) in male and female human participants, that the task-dependent modulation of the left ventral MGB (vMGB) for speech is particularly strong when recognizing speech in noisy listening conditions in contrast to situations where the speech signal is clear. The results imply that speech in noise recognition is supported by modifications at the level of the subcortical sensory pathway providing driving input to the auditory cortex.SIGNIFICANCE STATEMENT Speech recognition in noisy environments is a challenging everyday task. One reason why humans can master this task is the recruitment of additional cognitive resources as reflected in recruitment of non-language cerebral cortex areas. Here, we show that also modulation in the primary sensory pathway is specifically involved in speech in noise recognition. We found that the left primary sensory thalamus (ventral medial geniculate body; vMGB) is more involved when recognizing speech signals as opposed to a control task (speaker identity recognition) when heard in background noise versus when the noise was absent. This finding implies that the brain optimizes sensory processing in subcortical sensory pathway structures in a task-specific manner to deal with speech recognition in noisy environments.

Frequency response areas of neurons in the mouse inferior colliculus. III. Time-domain responses: Constancy, dynamics, and precision in relation to spectral resolution, and perception in the time domain.

The auditory midbrain (central nucleus of inferior colliculus, ICC) receives multiple brainstem projections and recodes auditory information for perception in higher centers. Many neural response characteristics are represented in gradients (maps) in the three-dimensional ICC space. Map overlap suggests that neurons, depending on their ICC location, encode information in several domains simultaneously by different aspects of their responses. Thus, interdependence of coding, e.g. in spectral and temporal domains, seems to be a general ICC principle. Studies on covariation of response properties and possible impact on sound perception are, however, rare. Here, we evaluated tone-evoked single neuron activity from the mouse ICC and compared shapes of excitatory frequency-response areas (including strength and shape of inhibition within and around the excitatory area; classes I, II, III) with types of temporal response patterns and first-spike response latencies. Analyses showed covariation of sharpness of frequency tuning with constancy and precision of responding to tone onsets. Highest precision (first-spike latency jitter < 1 ms) and stable phasic responses throughout frequency-response areas were the quality mainly of class III neurons with broad frequency tuning, least influenced by inhibition. Class II neurons with narrow frequency tuning and dominating inhibitory influence were unsuitable for time domain coding with high precision. The ICC center seems specialized rather for high spectral resolution (class II presence), lateral parts for constantly precise responding to sound onsets (class III presence). Further, the variation of tone-response latencies in the frequency-response areas of individual neurons with phasic, tonic, phasic-tonic, or pauser responses gave rise to the definition of a core area, which represented a time window of about 20 ms from tone onset for tone-onset responding of the whole ICC. This time window corresponds to the roughly 20 ms shortest time interval that was found critical in several auditory perceptual tasks in humans and mice.

Postnatal exposure to an acoustically enriched environment alters the morphology of neurons in the adult rat auditory system.

The structure of neurons in the central auditory system is vulnerable to various kinds of acoustic exposures during the critical postnatal developmental period. Here we explored long-term effects of exposure to an acoustically enriched environment (AEE) during the third and fourth weeks of the postnatal period in rat pups. AEE consisted of a spectrally and temporally modulated sound of moderate intensity, reinforced by a behavioral paradigm. At the age of 3-6 months, a Golgi-Cox staining was used to evaluate the morphology of neurons in the inferior colliculus (IC), the medial geniculate body (MGB), and the auditory cortex (AC). Compared to controls, rats exposed to AEE showed an increased mean dendritic length and volume and the soma surface in the external cortex and the central nucleus of the IC. The spine density increased in both the ventral and dorsal divisions of the MGB. In the AC, the total length and volume of the basal dendritic segments of pyramidal neurons and the number and density of spines on these dendrites increased significantly. No differences were found on apical dendrites. We also found an elevated number of spines and spine density in non-pyramidal neurons. These results show that exposure to AEE during the critical developmental period can induce permanent changes in the structure of neurons in the central auditory system. These changes represent morphological correlates of the functional plasticity, such as an improvement in frequency tuning and synchronization with temporal parameters of acoustical stimuli.

A Cortico-Collicular Amplification Mechanism for Gap Detection.

Auditory cortex (AC) is necessary for the detection of brief gaps in ongoing sounds, but not for the detection of longer gaps or other stimuli such as tones or noise. It remains unclear why this is so, and what is special about brief gaps in particular. Here, we used both optogenetic suppression and conventional lesions to show that the cortical dependence of brief gap detection hinges specifically on gap termination. We then identified a cortico-collicular gap detection circuit that amplifies cortical gap termination responses before projecting to inferior colliculus (IC) to impact behavior. We found that gaps evoked off-responses and on-responses in cortical neurons, which temporally overlapped for brief gaps, but not long gaps. This overlap specifically enhanced cortical responses to brief gaps, whereas IC neurons preferred longer gaps. Optogenetic suppression of AC reduced collicular responses specifically to brief gaps, indicating that under normal conditions, the enhanced cortical representation of brief gaps amplifies collicular gap responses. Together these mechanisms explain how and why AC contributes to the behavioral detection of brief gaps, which are critical cues for speech perception, perceptual grouping, and auditory scene analysis.

Disparity in interaural time difference improves the accuracy of neural representations of individual concurrent narrowband sounds in rat inferior colliculus and auditory cortex.

The central mechanisms underlying binaural unmasking for spectrally overlapping concurrent sounds, which are unresolved in the peripheral auditory system, remain largely unknown. In this study, frequency-following responses (FFRs) to two binaurally presented independent narrowband noises (NBNs) with overlapping spectra were recorded simultaneously in the inferior colliculus (IC) and auditory cortex (AC) in anesthetized rats. The results showed that for both IC FFRs and AC FFRs, introducing an interaural time difference (ITD) disparity between the two concurrent NBNs enhanced the representation fidelity, reflected by the increased coherence between the responses evoked by double-NBN stimulation and the responses evoked by single NBNs. The ITD disparity effect varied across frequency bands, being more marked for higher frequency bands in the IC and lower frequency bands in the AC. Moreover, the coherence between IC responses and AC responses was also enhanced by the ITD disparity, and the enhancement was most prominent for low-frequency bands and the IC and the AC on the same side. These results suggest a critical role of the ITD cue in the neural segregation of spectrotemporally overlapping sounds.NEW & NOTEWORTHY When two spectrally overlapped narrowband noises are presented at the same time with the same sound-pressure level, they mask each other. Introducing a disparity in interaural time difference between these two narrowband noises improves the accuracy of the neural representation of individual sounds in both the inferior colliculus and the auditory cortex. The lower frequency signal transformation from the inferior colliculus to the auditory cortex on the same side is also enhanced, showing the effect of binaural unmasking.

Neuronal sensitivity to the interaural time difference of the sound envelope in the mouse inferior colliculus.

We examined the sensitivity of the neurons in the mouse inferior colliculus (IC) to the interaural time differences (ITD) conveyed in the sound envelope. Utilizing optogenetic methods, we compared the responses to the ITD in the envelope of identified glutamatergic and GABAergic neurons. More than half of both cell types were sensitive to the envelope ITD, and the ITD curves were aligned at their troughs. Within the physiological ITD range of mice (±50 µs), the ITD curves of both cell types had a higher firing rate when the contralateral envelope preceded the ipsilateral envelope. These results show that the circuitry to process ITD persists in the mouse despite its lack of low-frequency hearing. The sensitivity of IC neurons to ITD is most likely to be shaped by the binaural interaction of excitation and inhibition in the lateral superior olive.

Tonotopic and non-auditory organization of the mouse dorsal inferior colliculus revealed by two-photon imaging.

The dorsal (DCIC) and lateral cortices (LCIC) of the inferior colliculus are major targets of the auditory and non-auditory cortical areas, suggesting a role in complex multimodal information processing. However, relatively little is known about their functional organization. We utilized in vivo two-photon Ca2+ imaging in awake mice expressing GCaMP6s in GABAergic or non-GABAergic neurons in the IC to investigate their spatial organization. We found different classes of temporal responses, which we confirmed with simultaneous juxtacellular electrophysiology. Both GABAergic and non-GABAergic neurons showed spatial microheterogeneity in their temporal responses. In contrast, a robust, double rostromedial-caudolateral gradient of frequency tuning was conserved between the two groups, and even among the subclasses. This, together with the existence of a subset of neurons sensitive to spontaneous movements, provides functional evidence for redefining the border between DCIC and LCIC.

A Temporal Filter for Binaural Hearing Is Dynamically Adjusted by Sound Pressure Level.

In natural environments our auditory system is exposed to multiple and diverse signals of fluctuating amplitudes. Therefore, to detect, localize, and single out individual sounds the auditory system has to process and filter spectral and temporal information from both ears. It is known that the overall sound pressure level affects sensory signal transduction and therefore the temporal response pattern of auditory neurons. We hypothesize that the mammalian binaural system utilizes a dynamic mechanism to adjust the temporal filters in neuronal circuits to different overall sound pressure levels. Previous studies proposed an inhibitory mechanism generated by the reciprocally coupled dorsal nuclei of the lateral lemniscus (DNLL) as a temporal neuronal-network filter that suppresses rapid binaural fluctuations. Here we investigated the consequence of different sound levels on this filter during binaural processing. Our in vivo and in vitro electrophysiology in Mongolian gerbils shows that the integration of ascending excitation and contralateral inhibition defines the temporal properties of this inhibitory filter. The time course of this filter depends on the synaptic drive, which is modulated by the overall sound pressure level and N-methyl-D-aspartate receptor (NMDAR) signaling. In psychophysical experiments we tested the temporal perception of humans and show that detection and localization of two subsequent tones changes with the sound pressure level consistent with our physiological results. Together our data support the hypothesis that mammals dynamically adjust their time window for sound detection and localization within the binaural system in a sound level dependent manner.

Intracochlear near infrared stimulation: Feasibility of optoacoustic stimulation in vivo.

Intracochlear optical stimulation has been suggested as an alternative approach to hearing prosthetics in recent years. This study investigated the properties of a near infrared laser (NIR) induced optoacoustic effect. Pressure recordings were performed at the external meatus of anaesthetized guinea pigs during intracochlear NIR stimulation. The sound pressure and power spectra were determined. The results were compared to multi unit responses in the inferior colliculus (IC). Additionally, the responses to NIR stimulation were compared to IC responses induced by intracochlear electric stimulation at the same cochlear position to investigate a potentially confounding contribution of direct neural NIR stimulation. The power spectra of the sound recorded at the external meatus (n = 7) had most power at frequencies below 10 kHz and showed little variation for different stimulation sites. The mean spike rates of IC units responding to intracochlear NIR stimulation (n = 222) of 17 animals were significantly correlated with the power of the externally recorded signal at frequencies corresponding to the best frequencies of the IC units. The response strength as well as the sound pressure at the external meatus depended on the pulse peak power of the optical stimulus. The sound pressure recorded at the external meatus reached levels above 70 dB SPL peak equivalent. In hearing animals a cochlear activation apical to the location of the fiber was found. The absence of any NIR responses after pharmacologically deafening and the comparison to electric stimulation at the NIR stimulation site revealed no indication of a confounding direct neural NIR stimulation. Intracochlear optoacoustic stimulation might become useful in combined electro-acoustic stimulation devices in the future.

Thalamocortical and Intracortical Inputs Differentiate Layer-Specific Mouse Auditory Corticocollicular Neurons.

Long-range descending projections from the auditory cortex play key roles in shaping response properties in the inferior colliculus. The auditory corticocollicular projection is massive and heterogeneous, with axons emanating from cortical layers 5 and 6, and plays a key role in directing plastic changes in the inferior colliculus. However, little is known about the cortical and thalamic networks within which corticocollicular neurons are embedded. Here, laser scanning photostimulation glutamate uncaging and photoactivation of channelrhodopsin-2 were used to probe the local and long-range network differences between preidentified layer 5 and layer 6 auditory corticocollicular neurons from male and female mice in vitro Layer 5 corticocollicular neurons were found to vertically integrate supragranular excitatory and inhibitory input to a substantially greater degree than their layer 6 counterparts. In addition, all layer 5 corticocollicular neurons received direct and large thalamic inputs from channelrhodopsin-2-labeled thalamocortical fibers, whereas such inputs were less common in layer 6 corticocollicular neurons. Finally, a new low-calcium/synaptic blockade approach to separate direct from indirect inputs using laser photostimulation was validated. These data demonstrate that layer 5 and 6 corticocollicular neurons receive distinct sets of cortical and thalamic inputs, supporting the hypothesis that they have divergent roles in modulating the inferior colliculus. Furthermore, the direct connection between the auditory thalamus and layer 5 corticocollicular neurons reveals a novel and rapid link connecting ascending and descending pathways.SIGNIFICANCE STATEMENT Descending projections from the cortex play a critical role in shaping the response properties of sensory neurons. The projection from the auditory cortex to the inferior colliculus is a massive, yet poorly understood, pathway emanating from two distinct cortical layers. Here we show, using a range of optical techniques, that mouse auditory corticocollicular neurons from different layers are embedded into different cortical and thalamic networks. Specifically, we observed that layer 5 corticocollicular neurons integrate information across cortical lamina and receive direct thalamic input. The latter connection provides a hyperdirect link between acoustic sensation and descending control, thus demonstrating a novel mechanism for rapid "online" modulation of sensory perception.

Hearing sensitivity evaluated by the auditory brainstem response in Miniopterus fuliginosus.

This study evaluated the hearing sensitivity of Miniopterus fuliginosus, a frequency-modulating (FM) bat species, by measuring the auditory brainstem responses in the inferior colliculus. The average audiogram was U-shaped. The mean threshold decreased gradually as the frequency increased from 16 to 40 kHz and then decreased rapidly as the frequency reached 46 kHz, with the peak sensitivity occurring at the terminal portion of the echolocation pulse between frequencies of 44 and 56 kHz. The shape of audiogram of M. fuliginosus is consistent with other FM bats, and is compared with its vocalization behavior.

Temporal Coding of Voice Pitch Contours in Mandarin Tones.

Accurate perception of time-variant pitch is important for speech recognition, particularly for tonal languages with different lexical tones such as Mandarin, in which different tones convey different semantic information. Previous studies reported that the auditory nerve and cochlear nucleus can encode different pitches through phase-locked neural activities. However, little is known about how the inferior colliculus (IC) encodes the time-variant periodicity pitch of natural speech. In this study, the Mandarin syllable /ba/ pronounced with four lexical tones (flat, rising, falling then rising and falling) were used as stimuli. Local field potentials (LFPs) and single neuron activity were simultaneously recorded from 90 sites within contralateral IC of six urethane-anesthetized and decerebrate guinea pigs in response to the four stimuli. Analysis of the temporal information of LFPs showed that 93% of the LFPs exhibited robust encoding of periodicity pitch. Pitch strength of LFPs derived from the autocorrelogram was significantly (p < 0.001) stronger for rising tones than flat and falling tones. Pitch strength are also significantly increased (p < 0.05) with the characteristic frequency (CF). On the other hand, only 47% (42 or 90) of single neuron activities were significantly synchronized to the fundamental frequency of the stimulus suggesting that the temporal spiking pattern of single IC neuron could encode the time variant periodicity pitch of speech robustly. The difference between the number of LFPs and single neurons that encode the time-variant F0 voice pitch supports the notion of a transition at the level of IC from direct temporal coding in the spike trains of individual neurons to other form of neural representation.

Frequency-specific attentional modulation in human primary auditory cortex and midbrain.

Paying selective attention to an audio frequency selectively enhances activity within primary auditory cortex (PAC) at the tonotopic site (frequency channel) representing that frequency. Animal PAC neurons achieve this 'frequency-specific attentional spotlight' by adapting their frequency tuning, yet comparable evidence in humans is scarce. Moreover, whether the spotlight operates in human midbrain is unknown. To address these issues, we studied the spectral tuning of frequency channels in human PAC and inferior colliculus (IC), using 7-T functional magnetic resonance imaging (FMRI) and frequency mapping, while participants focused on different frequency-specific sounds. We found that shifts in frequency-specific attention alter the response gain, but not tuning profile, of PAC frequency channels. The gain modulation was strongest in low-frequency channels and varied near-monotonically across the tonotopic axis, giving rise to the attentional spotlight. We observed less prominent, non-tonotopic spatial patterns of attentional modulation in IC. These results indicate that the frequency-specific attentional spotlight in human PAC as measured with FMRI arises primarily from tonotopic gain modulation, rather than adapted frequency tuning. Moreover, frequency-specific attentional modulation of afferent sound processing in human IC seems to be considerably weaker, suggesting that the spotlight diminishes toward this lower-order processing stage. Our study sheds light on how the human auditory pathway adapts to the different demands of selective hearing.

Differences between auditory frequency-following responses and onset responses: Intracranial evidence from rat inferior colliculus.

A periodic sound, such as a pure tone, evokes both transient onset field-potential responses and sustained frequency-following responses (FFRs) in the auditory midbrain, the inferior colliculus (IC). It is not clear whether the two types of responses are based on the same or different neural substrates. Although it has been assumed that FFRs are based on phase locking to the periodic sound, the evidence showing the direct relationship between the FFR amplitude and the phase-locking strength is still lacking. Using intracranial recordings from the rat central nucleus of inferior colliculus (ICC), this study was to examine whether FFRs and onset responses are different in sensitivity to pure-tone frequency and/or response-stimulus correlation, when a tone stimulus is presented either monaurally or binaurally. Particularly, this study was to examine whether the FFR amplitude is correlated with the strength of phase locking. The results showed that with the increase of tone-stimulus frequency from 1 to 2 kHz, the FFR amplitude decreased but the onset-response amplitude increased. Moreover, the FFR amplitude, but not the onset-response amplitude, was significantly correlated with the phase coherence between tone-evoked potentials and the tone stimulus. Finally, the FFR amplitude was negatively correlated with the onset-response amplitude. These results indicate that periodic-sound-evoked FFRs are based on phase-locking activities of sustained-response neurons, but onset responses are based on transient activities of onset-response neurons, suggesting that FFRs and onset responses are associated with different functions.

Processing of Natural Echolocation Sequences in the Inferior Colliculus of Seba's Fruit Eating Bat, Carollia perspicillata.

For the purpose of orientation, echolocating bats emit highly repetitive and spatially directed sonar calls. Echoes arising from call reflections are used to create an acoustic image of the environment. The inferior colliculus (IC) represents an important auditory stage for initial processing of echolocation signals. The present study addresses the following questions: (1) how does the temporal context of an echolocation sequence mimicking an approach flight of an animal affect neuronal processing of distance information to echo delays? (2) how does the IC process complex echolocation sequences containing echo information from multiple objects (multiobject sequence)? Here, we conducted neurophysiological recordings from the IC of ketamine-anaesthetized bats of the species Carollia perspicillata and compared the results from the IC with the ones from the auditory cortex (AC). Neuronal responses to an echolocation sequence was suppressed when compared to the responses to temporally isolated and randomized segments of the sequence. The neuronal suppression was weaker in the IC than in the AC. In contrast to the cortex, the time course of the acoustic events is reflected by IC activity. In the IC, suppression sharpens the neuronal tuning to specific call-echo elements and increases the signal-to-noise ratio in the units' responses. When presenting multiple-object sequences, despite collicular suppression, the neurons responded to each object-specific echo. The latter allows parallel processing of multiple echolocation streams at the IC level. Altogether, our data suggests that temporally-precise neuronal responses in the IC could allow fast and parallel processing of multiple acoustic streams.

Midbrain adaptation may set the stage for the perception of musical beat.

The ability to spontaneously feel a beat in music is a phenomenon widely believed to be unique to humans. Though beat perception involves the coordinated engagement of sensory, motor and cognitive processes in humans, the contribution of low-level auditory processing to the activation of these networks in a beat-specific manner is poorly understood. Here, we present evidence from a rodent model that midbrain preprocessing of sounds may already be shaping where the beat is ultimately felt. For the tested set of musical rhythms, on-beat sounds on average evoked higher firing rates than off-beat sounds, and this difference was a defining feature of the set of beat interpretations most commonly perceived by human listeners over others. Basic firing rate adaptation provided a sufficient explanation for these results. Our findings suggest that midbrain adaptation, by encoding the temporal context of sounds, creates points of neural emphasis that may influence the perceptual emergence of a beat.