Auditory Midbrain Neurons Research Articles

Mixed Representations of Sound and Action in the Auditory Midbrain.

Linking sensory input and its consequences is a fundamental brain operation. During behavior, the neural activity of neocortical and limbic systems often reflects dynamic combinations of sensory and task-dependent variables, and these "mixed representations" are suggested to be important for perception, learning, and plasticity. However, the extent to which such integrative computations might occur outside of the forebrain is less clear. Here, we conduct cellular-resolution two-photon Ca2+ imaging in the superficial "shell" layers of the inferior colliculus (IC), as head-fixed mice of either sex perform a reward-based psychometric auditory task. We find that the activity of individual shell IC neurons jointly reflects auditory cues, mice's actions, and behavioral trial outcomes, such that trajectories of neural population activity diverge depending on mice's behavioral choice. Consequently, simple classifier models trained on shell IC neuron activity can predict trial-by-trial outcomes, even when training data are restricted to neural activity occurring prior to mice's instrumental actions. Thus, in behaving mice, auditory midbrain neurons transmit a population code that reflects a joint representation of sound, actions, and task-dependent variables.

Spatial separation between two sounds affects the timing of action potentials elicited by the sounds in the rat's auditory midbrain neurons

Timing of action potentials (i.e., spikes) elicited by sounds is used by auditory neurons to encode and process acoustic information. In the presence of multiple sounds, the timing of sound-driven spikes is dependent on the temporal, spectral, and spatial relationships among the sounds. We used two tone bursts with different frequencies to form a train of stimuli that were presented at a random odor and a constant rate. Such a train was used to mimic two competing sounds that occurred at the same (50%) probability or a novel sound (i.e., a low probability oddball sound) that was interleaved with a frequently occurring background sound (i.e., a high probability standard sound). We used the rat as an animal model to study how the spatial relationship between two sounds affected the timing of spikes elicited by the sounds in individual neurons in the auditory midbrain. Results indicate that a lower probability of sound presentation led to a higher temporal precision of the timing of the first spike elicited by the sound and the timing could be affected by a spatial separation between two sounds. These results are important for understanding neural mechanisms responsible for hearing in a natural acoustic environment.

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. A potential substrate for top-down predictive cues is the massive set of descending projections from the cortex to subcortical structures, although the role of these corticofugal neurons 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 auditory midbrain neurons to stimuli designed to test prediction error and repetition suppression. Inactivation of the cortico-collicular pathway led to a decrease in prediction error and repetition enhancement in these neurons. Overall, our results demonstrate that the auditory cortex provides cues about the statistical context of sound to subcortical brain regions via direct feedback, regulating processing of both prediction and repetition.

Neural coding of dichotic pitches in auditory midbrain.

Dichotic pitches such as the Huggins pitch (HP) and the binaural edge pitch (BEP) are perceptual illusions whereby binaural noise that exhibits abrupt changes in interaural phase differences (IPDs) across frequency creates a tonelike pitch percept when presented to both ears, even though it does not produce a pitch when presented monaurally. At the perceptual and cortical levels, dichotic pitches behave as if an actual tone had been presented to the ears, yet investigations of neural correlates of dichotic pitch in single-unit responses at subcortical levels are lacking. We tested for cues to HP and BEP in the responses of binaural neurons in the auditory midbrain of anesthetized cats by varying the expected pitch frequency around each neuron's best frequency (BF). Neuronal firing rates showed specific features (peaks, troughs, or edges) when the pitch frequency crossed the BF, and the type of feature was consistent with a well-established model of binaural processing comprising frequency tuning, internal delays, and firing rates sensitive to interaural correlation. A Jeffress-like neural population model in which the behavior of individual neurons was governed by the cross-correlation model and the neurons were independently distributed along BF and best IPD predicted trends in human psychophysical HP detection but only when the model incorporated physiological BF and best IPD distributions. These results demonstrate the existence of a rate-place code for HP and BEP in the auditory midbrain and provide a firm physiological basis for models of dichotic pitches.NEW & NOTEWORTHY Dichotic pitches are perceptual illusions created centrally through binaural interactions that offer an opportunity to test theories of pitch and binaural hearing. Here we show that binaural neurons in auditory midbrain encode the frequency of two salient types of dichotic pitches via specific features in the pattern of firing rates along the tonotopic axis. This is the first combined single-unit and modeling study of responses of auditory neurons to stimuli evoking a dichotic pitch.

Target ranging by echolocation in bats: Performance and mechanisms

James Simmons’s early research on sonar ranging in echolocating bats generated two groundbreaking discoveries: (1) Bats compute object distance from the time delay between sonar calls and echoes, and they discriminate echo-delay differences in the microsecond range [Simmons, https://psycnet.apa.org/doi/10.1121/1.1913559 (1973)] and (2) A population of auditory neurons show facilitated and echo delay-tuned responses, a posited neural substrate of sonar ranging [Feng et al., https://10.1126/science.705350 (1978)]. These findings spawned decades of biosonar research around the world, and this talk will summarize three new findings on the mechanisms of sonar ranging in the big brown bat, Eptesicus fuscus. (1) Echo-delay tuned neurons in the midbrain of the free-flying bat show 3D spatial tuning to echoes from physical objects, and sonar-guided attention evokes sharper delay-dependent response areas and shifts to shorter echo delays. (2) Local field potential recordings from auditory midbrain neurons in the passively listening bat encode the time interval between call-echo pairs in the microsecond range, with accuracy dependent on signal duration and bandwidth. (3) A population of hippocampal CA1 neurons encodes the distance of sonar objects in bats as they track moving targets, and responses of hippocampal neurons depend on the production of sonar calls that yield echo returns.

Oscillatory discharges in the auditory midbrain of the big brown bat contribute to coding of echo delay.

Subsequent to his breakthrough discovery of delay-tuned neurons in the bat's auditory midbrain and cortex, Albert Feng proposed that neural computations for echo delay involve intrinsic oscillatory discharges generated in the inferior colliculus (IC). To explore further the presence of these neural oscillations, we recorded multiple unit activity with a novel annular low impedance electrode from the IC of anesthetized big brown bats and Seba's short-tailed fruit bats. In both species, responses to tones, noise bursts, and FM sweeps contain long latency components, extending up to 60ms post-stimulus onset, organized in periodic, oscillatory-like patterns at frequencies of 360-740Hz. Latencies of this oscillatory activity resemble the wide distributions of single neuron response latencies in the IC. In big brown bats, oscillations lasting up to 30ms after pulse onset emerge in response to single FM pulse-echo pairs, at particular pulse-echo delays. Oscillatory responses to pulses and evoked responses to echoes overlap extensively at short echo delays (5-7ms), creating interference-like patterns. At longer echo delays, responses are separately evident to both pulses and echoes, with less overlap. These results extend Feng's reports of IC oscillations, and point to different processing mechanisms underlying perception of short vs long echo delays.

Diversity of temporal response patterns in midbrain auditory neurons of frogs Batrachyla and its relevance for male vocal responses.

We investigated response selectivities of single auditory neurons in the torus semicircularis of male frogs Batrachyla leptopus (72 neurons) and B. taeniata (57 neurons) to synthetic stimuli of different temporal structures. Series of stimuli in which note and pulse rate, note and pulse structure and call duration varied systematically were presented. Neuronal responses quantified in terms of proportions of units displaying diverse temporal transfer functions are related in different modes with patterns of evoked vocal responses studied previously in these frogs. Correspondences and mismatches occurred between the auditory and vocal domains. The analysis of this evidence together with corresponding information from previous neuronal and behavioral studies in the third species of this genus, B. antartandica, indicates that different modes of preferences for acoustic communication signals can coexist within this anuran group.

Strong energy component is more important than spectral selectivity in modeling responses of midbrain auditory neurons to wide-band environmental sounds

Modeling central auditory neurons in response to complex sounds not only helps understanding neural processing of speech signals but can also provide insights for biomimetics in neuro-engineering. While modeling responses of midbrain auditory neurons to synthetic tones is rather good, modeling those to environmental sounds is less satisfactory. Environmental sounds typically contain a wide range of frequency components, often with strong and transient energy. These stimulus features have not been examined in the conventional approach of auditory modeling centered on spectral selectivity. To this end, we firstly compared responses to an environmental sound of auditory midbrain neurons across 3 subpopulations of neurons with frequency selectivity in the low, middle and high ranges; secondly, we manipulated the sound energy, both in power and in spectrum, and compared across these subpopulations how their modeled responses were affected. The environmental sound was recorded when a rat was drinking from a feeding bottle (called the ‘drinking sound’). The sound spectrum was divided into 20 non-overlapping frequency bands (from 0 to 20 kHz, at 1 kHz width) and presented to an artificial neural model built on a committee machine with parallel spectral inputs to simulate the known tonotopic organization of the auditory system. The model was trained to predict empirical response probability profiles of neurons to the repeated sounds. Results showed that model performance depended more on the strong energy components than on the spectral selectivity. Findings were interpreted to reflect general sensitivity to rapidly changing sound intensities at the auditory midbrain and in the cortex.

Extensions of a neural-fluctuation perspective on simultaneous notched-noise masking

A previous paper [Maxwell et al., J. Acoust. Soc. Am. 3523, 3537 (2020)] suggested that listeners may identify the target interval in a simultaneous notched-noise task using neural fluctuations, which change with the addition of a tone to the masker. Neural fluctuations are changes in the instantaneous firing rate of auditory-nerve fibers, generally at a longer (slower) time scale than temporal fine structure, that are shaped by peripheral nonlinearities. Differences in neural-fluctuation amplitudes across the peripheral tonotopic axis are proposed to lead to differences in rates across the population of auditory midbrain neurons, due to the sensitivity of these neurons to amplitude modulation. Here, using similar methods to Maxwell et al. (2020) and stimuli matching those of Baker and Rosen (J.Ascoust. Soc. Am. 454, 462 (2006)], we extend previous work by demonstrating that neural fluctuations may account for additional features of simultaneous notched-noise masking results. These features include (1) increase in filter bandwidth at higher stimulus frequencies, (2) higher bandwidth with increasing masker level, and (3) filter asymmetry. These results, in conjunction with the previous conclusion that auditory-nerve excitation patterns cannot explain notched-noise thresholds in all cases, support the interpretation that psychophysical auditory filters may be based on the output of the subcortical auditory system. [Work supported by NIDCD-R01-010813.]

Temporary Unilateral Hearing Loss Impairs Spatial Auditory Information Processing in Neurons in the Central Auditory System.

Temporary conductive hearing loss (CHL) can lead to hearing impairments that persist beyond resolution of the CHL. In particular, unilateral CHL leads to deficits in auditory skills that rely on binaural input (e.g., spatial hearing). Here, we asked whether single neurons in the auditory midbrain, which integrate acoustic inputs from the two ears, are altered by a temporary CHL. We introduced 6 weeks of unilateral CHL to young adult chinchillas via foam earplug. Following CHL removal and restoration of peripheral input, single-unit recordings from inferior colliculus (ICC) neurons revealed the CHL decreased the efficacy of inhibitory input to the ICC contralateral to the earplug and increased inhibitory input ipsilateral to the earplug, effectively creating a higher proportion of monaural responsive neurons than binaural. Moreover, this resulted in a ∼10 dB shift in the coding of a binaural sound location cue (interaural-level difference, ILD) in ICC neurons relative to controls. The direction of the shift was consistent with a compensation of the altered ILDs due to the CHL. ICC neuron responses carried ∼37% less information about ILDs after CHL than control neurons. Cochlear peripheral-evoked responses confirmed that the CHL did not induce damage to the auditory periphery. We find that a temporary CHL altered auditory midbrain neurons by shifting binaural responses to ILD acoustic cues, suggesting a compensatory form of plasticity occurring by at least the level of the auditory midbrain, the ICC.

Rescuing Auditory Temporal Processing with a Novel Augmented Acoustic Environment in an Animal Model of Congenital Hearing Loss.

Congenital sensorineural hearing loss (SNHL) affects thousands of infants each year and results in significant delays in speech and language development. Previous studies have shown that early exposure to a simple augmented acoustic environment (AAE) can limit the effects of progressive SNHL on hearing sensitivity. However, SNHL is also accompanied by hearing loss that is not assessed on standard audiological examinations, such as reduced temporal processing acuity. To assess whether sound therapy may improve these deficits, a mouse model of congenital SNHL was exposed to simple or temporally complex AAE. The DBA/2J mouse strain develops rapid, base to apex, progressive SNHL beginning at birth and is functionally deaf by six months of age. Hearing sensitivity and auditory brainstem function was measured using otoacoustic emissions, auditory brainstem response (ABR) and extracellular recording from the inferior colliculus (IC) in mice following exposure to 30 d of continuous AAE. Peripheral function and sound sensitivity in auditory midbrain neurons improved following exposure to both types of AAE. However, exposure to a novel, temporally complex AAE more strongly improved a measure of temporal processing acuity, neural gap-in-noise detection in the auditory midbrain. These experiments suggest that targeted sound therapy may be harnessed to improve hearing outcomes for children suffering from congenital SNHL.

Constant Resting Frequency and Auditory Midbrain Neuronal Frequency Analysis of Hipposideros pratti in Background White Noise.

Acoustic communication signals are inevitably challenged by ambient noise. In response to noise, many animals adjust their calls to maintain signal detectability. However, the mechanisms by which the auditory system adapts to the adjusted pulses are unclear. Our previous study revealed that the echolocating bat, Hipposideros pratti, increased its pulse intensity in the presence of background white noise. In vivo single-neuron recording demonstrated that the auditory midbrain neurons tuned to the second harmonic (H2 neurons) increased their minimal threshold (MT) to a similar degree as the increment of pulse intensity in the presence of the background noise. Furthermore, the H2 neurons exhibited consistent spike rates at their best amplitudes and sharper intensity tuning with background white noise compared with silent conditions. The previous data indicated that sound intensity analysis by auditory midbrain neurons was adapted to the increased pulse intensity in the same noise condition. This study further examined the echolocation pulse frequency and frequency analysis of auditory midbrain neurons with noise conditions. The data revealed that H. pratti did not shift the resting frequency in the presence of background noise. The auditory midbrain neuronal frequency analysis highly linked to processing the resting frequency with the presence of noise by presenting the constant best frequency (BF), frequency sensitivity, and frequency selectivity. Thus, our results suggested that auditory midbrain neuronal responses in background white noise are adapted to process echolocation pulses in the noise conditions.

The second harmonic neurons in auditory midbrain of Hipposideros pratti are more tolerant to background white noise

Although acoustic communication is inevitably influenced by noise, behaviorally relevant sounds are perceived reliably. The noise-tolerant and -invariant responses of auditory neurons are thought to be the underlying mechanism. So, it is reasonable to speculate that neurons with best frequency tuned to behaviorally relevant sounds will play important role in noise-tolerant perception. Echolocating bats live in groups and emit multiple harmonic signals and analyze the returning echoes to extract information about the target features, making them prone to deal with noise in their natural habitat. The echolocation signal of Hipposideros pratti usually contains 3–4 harmonics (H1H4), the second harmonic has the highest amplitude and is thought to play an essential role during echolocation behavior. Therefore, it is reasonable to propose that neurons tuned to the H2, named the H2 neurons, can be more noise-tolerant to background noise. Taking advantage of bat's stereotypical echolocation signal and single-cell recording, our present study showed that the minimal threshold increases (12.2 dB) of H2 neurons in the auditory midbrain were comparable to increase in bat's call intensity (14.2 dB) observed in 70 dB SPL white noise condition, indicating that the H2 neurons could work as background noise monitor. The H2 neurons had higher minimal thresholds and sharper frequency tuning, which enabled them to be more tolerant to background noise. Furthermore, the H2 neurons had consistent best amplitude spikes and sharper intensity tuning in background white noise condition than in silence. Taken together, these results suggest that the H2 neurons might account for noise-tolerant perception of behaviorally relevant sounds.

How auditory selectivity for sound timing arises: The diverse roles of GABAergic inhibition in shaping the excitation to interval-selective midbrain neurons.

Across sensory systems, temporal frequency information is progressively transformed along ascending central pathways. Despite considerable effort to elucidate the mechanistic basis of these transformations, they remain poorly understood. Here we used a novel constellation of approaches, including whole-cell recordings and focal pharmacological manipulation, in vivo, and new computational algorithms that identify conductances resulting from excitation, inhibition and active membrane properties, to elucidate the mechanisms underlying the selectivity of midbrain auditory neurons for long temporal intervals. Surprisingly, we found that stimulus-driven excitation can be increased and its selectivity decreased following attenuation of inhibition with gabazine or intracellular delivery of fluoride. We propose that this nonlinear interaction is due to shunting inhibition. The rate-dependence of this inhibition results in the illusion that excitation to a cell shows greater temporal selectivity than is actually the case. We also show that rate-dependent depression of excitation, an important component of long-interval selectivity, can be decreased after attenuating inhibition. These novel findings indicate that nonlinear shunting inhibition plays a key role in shaping the amplitude and interval selectivity of excitation. Our findings provide a major advance in understanding how the brain decodes intervals and may explain paradoxical temporal selectivity of excitation to midbrain neurons reported previously.

Foreground stimuli and task engagement enhance neuronal adaptation to background noise in the inferior colliculus of macaques.

Auditory neuronal responses are modified by background noise. Inferior colliculus (IC) neuronal responses adapt to the most frequent sound level within an acoustic scene (adaptation to stimulus statistics), a mechanism that may preserve neuronal and behavioral thresholds for signal detection. However, it is still unclear whether the presence of foreground stimuli and/or task involvement can modify neuronal adaptation. To investigate how task engagement interacts with this mechanism, we compared the response of IC neurons to background noise, which caused adaptation to stimulus statistics, while macaque monkeys performed a masked tone detection task (task-driven condition) with responses recorded when the same background noise was presented alone (passive listening condition). In the task-dependent condition, monkeys performed a Go/No-Go task while 50-ms tones were embedded within an adaptation-inducing continuous background noise whose levels changed every 50 ms and were drawn from a probability distribution. The adaptation to noise stimulus statistics in IC neuronal responses was significantly enhanced in the task-driven condition compared with the passive listening condition, showing that foreground stimuli and/or task-engagement can modify IC neuronal responses. Additionally, the response of IC neurons to noise was significantly affected by the preceding sensory information (history effect) regardless of task involvement. These studies show that dynamic range adaptation in IC preserves behavioral and neurometric thresholds irrespective of noise type and a dependence of neuronal activity on task-related factors at subcortical levels of processing.NEW & NOTEWORTHY Auditory neuronal responses are influenced by maskers and distractors. However, it is still unclear whether the neuronal sensitivity to the masker stimulus is influenced by task-dependent factors. Our study represents one of the first attempts to investigate how task involvement influences the neural representation of background sounds in the subcortical, midbrain auditory neurons of behaving animals.

Specialization of Neurons with Different Response Patterns in the Mouse Mus musculus Auditory Midbrain and Primary Auditory Cortex during Communication Call Processing

Wriggling call produced by mouse pups when struggling in the nest is one of the mouse early ontogenesis communicative vocalization. Processing of these signals by auditory midbrain and primary auditory cortex neurons with different response patterns was the subject of this study. Responses of single neurons evoked by wriggling call models and a series of models consisting of 4 stimuli with different interstimulus intervals (0–1000 ms) were recorded extracellularly. A third of central nucleus neurons in the inferior colliculus showed a spectral facilitation in responses to various two- and three-tone combinations of the wriggling call frequency components. About 80% of such combination-sensitive neurons had tonic characteristics of responses, i.e. tonic, phasic-tonic, pauser and long-latency discharges. A study of responses of central nucleus neurons to a series of wriggling call models showed that at short interstimulus intervals (0–50 ms) responses to the 2nd–4th signals in a series were completely suppressed or significantly decreased in two-thirds of the recorded neurons, i.e. there arose adaptation to a series of sounds. Such neurons had mainly phasic discharges. In a third of neurons, adaptation did not arise; these neurons were tonically discharging. All neurons in the primary auditory cortex (anterior and primary auditory fields) demonstrated adaptation in responses to a series of wriggling calls. Discharges of neurons were phasic.

Specific loss of neural sensitivity to interaural time difference of unmodulated noise stimuli following noise-induced hearing loss.

Sensorineural hearing loss (SNHL) causes an overall deficit in binaural hearing, including the abilities to localize sound sources, discriminate interaural time and level differences (ITDs and ILDs, respectively), and utilize binaural cues to aid signal detection and comprehension in noisy environments. Few studies have examined the effect of SNHL on binaural coding in the central auditory system, and those that have focused on age-related hearing loss. We induced hearing loss in male and female Dutch-belted rabbits via noise overexposure and compared unanesthetized single-unit responses of their inferior colliculi [hearing loss (HL) neurons] with those of unexposed rabbits. Sound-level thresholds of HL neurons to diotic noise were elevated by 75 dB, on average. Sensitivity of firing rates of HL neurons to the azimuth of a broadband noise stimulus was reduced, on average, but was confounded by differences in sound level with respect to detection threshold between groups. We independently manipulated ITD and ILD in virtual acoustic space and found directional sensitivity in binaurally sensitive HL neurons was entirely due to ILD sensitivity and no different than that for unexposed rabbits. However, ITD sensitivity was completely absent in binaurally sensitive HL neurons for noise stimuli both in virtual acoustic space and with ITDs extending to ±3 ms. HL neurons also had weaker spike-timing precision and slightly increased spontaneous rates. Overall, ILD sensitivity was uncompromised, whereas ITD sensitivity was completely lost, implying a specific inability to use information in the timing or correlation of acoustic noise waveforms between the two ears following severe SNHL.NEW & NOTEWORTHY Sensorineural hearing loss compromises perceptual abilities that arise from hearing with two ears, yet its effects on binaural aspects of neural responses are largely unknown. We found that, following severe hearing loss because of acoustic trauma, auditory midbrain neurons specifically lost the ability to encode time differences between the arrival of a broadband noise stimulus to the two ears, whereas the encoding of sound level differences between the two ears remained uncompromised.

Developmentally Regulated Rebound Depolarization Enhances Spike Timing Precision in Auditory Midbrain Neurons.

The inferior colliculus (IC) is an auditory midbrain structure involved in processing biologically important temporal features of sounds. The responses of IC neurons to these temporal features reflect an interaction of synaptic inputs and neuronal biophysical properties. One striking biophysical property of IC neurons is the rebound depolarization produced following membrane hyperpolarization. To understand how the rebound depolarization is involved in spike timing, we made whole-cell patch clamp recordings from IC neurons in brain slices of P9–21 rats. We found that the percentage of rebound neurons was developmentally regulated. The precision of the timing of the first spike on the rebound increased when the neuron was repetitively injected with a depolarizing current following membrane hyperpolarization. The average jitter of the first spikes was only 0.5 ms. The selective T-type Ca2+ channel antagonist, mibefradil, significantly increased the jitter of the first spike of neurons in response to repetitive depolarization following membrane hyperpolarization. Furthermore, the rebound was potentiated by one to two preceding rebounds within a few hundred milliseconds. The first spike generated on the potentiated rebound was more precise than that on the non-potentiated rebound. With the addition of a calcium chelator, BAPTA, into the cell, the rebound potentiation no longer occurred, and the precision of the first spike on the rebound was not improved. These results suggest that the postinhibitory rebound mediated by T-type Ca2+ channel promotes spike timing precision in IC neurons. The rebound potentiation and precise spikes may be induced by increases in intracellular calcium levels.

Spatial Separation between Two Sounds of an Oddball Paradigm Affects Responses of Neurons in the Rat’s Inferior Colliculus to the Sounds

The ability to sense occasionally occurring sounds in an environment is critical for animals. To understand this ability, we studied responses to acoustic oddball paradigms in the rat’s midbrain auditory neurons. An oddball paradigm is a random sequence of stimuli created using two tone bursts, with one presented at a high probability (standard stimulus) and the other at a low probability (oddball stimulus). The sounds were either colocalized at the ear contralateral to a neuron under investigation (c90° azimuth) or separated with one at c90° while the other at another azimuth. We found that most neurons generated stronger responses to a sound at c90° when it was presented as an oddball than as a standard stimulus. Relocating one sound from c90° to another azimuth changed both responses to the relocated sound and the sound that remained at c90°. Most notably, the response to an oddball stimulus at c90° was increased when a standard stimulus was relocated from c90° to a location that was in front of the animal or on the ipsilateral side of recording. The increase was particularly large in neurons that displayed transient firing under contralateral stimulation but no firing under ipsilateral stimulation. These neurons likely play a particularly important role in using spatial cues to detect occasionally occurring sounds. Results suggest that effects of spatial separation between two sounds of an oddball paradigm on responses to the sounds were dependent on changes in the level of adaptation and binaural inhibition.

Dopamine modulates subcortical responses to surprising sounds.

Dopamine guides behavior and learning through pleasure, according to classic understanding. Dopaminergic neurons are traditionally thought to signal positive or negative prediction errors (PEs) when reward expectations are, respectively, exceeded or not matched. These signed PEs are quite different from the unsigned PEs, which report surprise during sensory processing. But mounting theoretical accounts from the predictive processing framework postulate that dopamine, as a neuromodulator, could potentially regulate the postsynaptic gain of sensory neurons, thereby scaling unsigned PEs according to their expected precision or confidence. Despite ample modeling work, the physiological effects of dopamine on the processing of surprising sensory information are yet to be addressed experimentally. In this study, we tested how dopamine modulates midbrain processing of unexpected tones. We recorded extracellular responses from the rat inferior colliculus to oddball and cascade sequences, before, during, and after the microiontophoretic application of dopamine or eticlopride (a D2-like receptor antagonist). Results demonstrate that dopamine reduces the net neuronal responsiveness exclusively to unexpected sensory input without significantly altering the processing of expected input. We conclude that dopaminergic projections from the thalamic subparafascicular nucleus to the inferior colliculus could encode the expected precision of unsigned PEs, attenuating via D2-like receptors the postsynaptic gain of sensory inputs forwarded by the auditory midbrain neurons. This direct dopaminergic modulation of sensory PE signaling has profound implications for both the predictive coding framework and the understanding of dopamine function.