Central Nucleus Of The Inferior Colliculus Research Articles

5-Hydroxytryptamine 2A receptors of the dorsal raphe nucleus modulate panic-like behaviours and mediate fear-induced antinociception elicited by neuronal activation in the central nucleus of the inferior colliculus

It has been established that chemical stimulation of the inferior colliculus (IC) of laboratory animals evokes fear-related defensive responses, which are considered panic attack-like behaviours. In addition, there is evidence that defensive reactions provoked by chemical stimulation of midbrain tectum neurons may induce an antinociceptive response. Morphologically, the IC receives projections from other mesencephalic structures, such as the dorsal raphe nucleus (DRN), a region rich in serotonergic neurons that play a critical role in the control of defensive behaviours. Moreover, this monoaminergic brainstem reticular nucleus is suggested to comprise the endogenous pain modulatory system. The aim of the present study was to investigate the role of DRN 5-hydroxytryptamine 2A (5-HT2A) receptors in Wistar rats by local microinjection of R-96544 (a selective antagonist of the 5-HT2A receptor) at doses of 5, 10 or 15 nM on defensive reactions and fear-induced antinociception evoked by chemical stimulation of the central nucleus of the IC with NMDA (6, 9 or 12 nmol). Behavioural responses were analysed for 10 min, and then the nociceptive threshold was measured at 10 min intervals for 70 min. The dose of 12 nmol of NMDA was the most effective in causing panic attack-like defensive behaviours and much higher hypoalgesia. In addition, both effects were attenuated by pretreatment of the DRN with R-96544. These findings suggest the critical participation of DRN 5-HT2A receptors in the modulation of panic attack-like defensive behaviour and unconditioned fear-induced antinociception organised by neurons in the central nucleus of the IC.

Influence of behavioral state on auditory processing in the marmoset midbrain

Recent work shows that neurons in the inferior colliculus (IC) undergo receptive field changes during auditory behavior in ferrets (Slee & David, 2015. J. Neurosci.). In this study, we tested for similar effects in the marmoset monkey, a highly vocal primate species. We trained two marmosets to detect a pure tone target embedded in a background of random spectral shape (RSS) distractor stimuli. We recorded single-unit activity in the central nucleus of the IC (ICC). Neural responses to targets and distractors were compared between conditions when the marmoset performed the detection task or listened passively. When target frequency was near the neuronal best frequency (BF), responses to distractors were suppressed in about half of the neurons during behavior. Target responses were modulated in some neurons but suppression or enhancement was equally likely. We also measured effects of task engagement in non-central divisions of the IC (NCIC). There, target responses were strongly enhanced during behavior in about half of neurons in this region (median change = 70%). We also found a subset of NCIC neurons that responded with increased firing following the target sound, possibly encoding a reward-related signal. This study replicates our previous finding that distractor responses are suppressed during auditory behavior in the ferret IC. In addition, we found an area in the NCIC with large enhancement of target responses during behavior, suggesting that task engagement produces distinct effects across subdivisions of the IC.

Dorsal pallidal neurons directly link the nidopallium and midbrain in the zebra finch (Taeniopygia guttata).

The dorsal pallidum in birds is considered similar, if not homologous, to the globus pallidus (GP) of mammals. The dorsal pallidum projects to both thalamic and midbrain targets similar to the direct and indirect pathways arising from the internal and external segments of the GP. In the present study, retrograde and anterograde tracing studies revealed a previously undescribed projection of the avian dorsal pallidum. This arises from a specific dorsomedial component, which terminates in the intercollicular nucleus and partly surrounds the avian equivalent of the central nucleus of the inferior colliculus. The respiratory-vocal dorsomedial nucleus of the intercollicular complex, however, does not receive these projections. The somata of the pallidal neurons retrogradely labeled from injections in the intercollicular nucleus were large and generally multipolar and had extensive, sparsely branching central processes (presumptive dendrites) that together extended up to 2 mm dorsally into the intermediate and caudomedial nidopallium. The size and morphology of these neurons were similar to those of large pallidal neurons labeled by calretinin immunoreactivity, which could be co-localized to the same cells. Thus, rather than being directly involved in the control of movement, the large dorsomedial neurons of the caudal dorsal pallidum may be involved in sensory processing, in that they provide an unusual direct link between sensory (auditory/somatosensory) regions of the nidopallium and sensory regions of the intercollicular nucleus of the midbrain. J. Comp. Neurol. 525:1731-1742, 2017. © 2016 Wiley Periodicals, Inc.

Abnormal Expression of MicroRNAs Induced by Chronic Unpredictable Mild Stress in Rat Hippocampal Tissues.

Previous research has demonstrated that the behaviors observed in chronic unpredictable mild stressed (CUMS) rats are similar to the symptoms of depressed patients and that the abnormal expression of cerebral microRNAs is associated with depressive disorder. However, little is known regarding the expression profile of microRNAs induced by CUMS. In this study, we aimed to examine the hippocampal microRNA expression profile in CUMS rats. Forty adolescent male Sprague-Dawley rats were randomly divided into normal and model groups. The rats in the model group were stimulated daily with randomly applied mild stressors from among 14 different mild stressors. The stressors were changed every day and were applied for 35 consecutive days. On the 28th and 35th days after treatment, the weights, physical condition, sucrose preference, and open-field test scores of the rats of the two groups were evaluated. Successful induction of CUMS was considered if the differences of the above metrics between the two groups were statistically significant on the 28th and 35th days after treatment. Cerebral sucrose metabolism images of rats were obtained by 18F-FDG PET/CT. The rats were euthanized under anesthesia, and hippocampal tissues were collected for hematoxylin-eosin (HE) staining. In addition, the samples were used for microRNA array chip and qRT-PCR analysis. The target genes of different microRNAs were predicted using bioinformatic analysis, and the functions and signal pathways of these target genes were investigated by GO and KEGG analyses. Sixteen rats exhibited successful induction of CUMS. Cerebral 18F-FDG PET/CT imaging showed that the glucose metabolism rate of CUMS rats were significantly lower than normal rats in the central nucleus of the inferior colliculus (CIC, p=0.022), the retrosplenial agranular area (RSA, p=0.002), the second sensory cortex (S2, p=0.028), the first auditory cortex (Au1, p=0.012), the primary somatosensory cortex, barrel field (SIBF, p=0.001), and the ventral posteromedial nucleus (VPM) of the right thalamus (p=0.048). HE staining showed that hippocampal pyramidal cells CUMS rats were thinner, disordered, and exhibited irregular shapes, with many pyknotic cells. The microarray chip and qRT-PCR analysis revealed that five microRNAs were significantly up-regulated [miR-382-3p (p=0.026), miR-183-5p (p=0.018), miR-3573-5p (p=0.042), miR-202-3p (p=0.016), miR-493-3p (p=0.009)], and only miR-370-3p was significantly down-regulated (p=0.036). miRNA target gene prediction and functional annotation analysis showed significant enrichment in several GO terms and pathways associated with depression. Our findings provide supportive evidence for the abnormal expression of multiple CUMS-induced hippocampal microRNAs in rats as well as the involvement of these microRNAs in depressive disorder.

Spectral summation and facilitation in on- and off-responses for optimized representation of communication calls in mouse inferior colliculus.

Selectivity for processing of species-specific vocalizations and communication sounds has often been associated with the auditory cortex. The midbrain inferior colliculus, however, is the first center in the auditory pathways of mammals integrating acoustic information processed in separate nuclei and channels in the brainstem and, therefore, could significantly contribute to enhance the perception of species' communication sounds. Here, we used natural wriggling calls of mouse pups, which communicate need for maternal care to adult females, and further 15 synthesized sounds to test the hypothesis that neurons in the central nucleus of the inferior colliculus of adult females optimize their response rates for reproduction of the three main harmonics (formants) of wriggling calls. The results confirmed the hypothesis showing that average response rates, as recorded extracellularly from single units, were highest and spectral facilitation most effective for both onset and offset responses to the call and call models with three resolved frequencies according to critical bands in perception. In addition, the general on- and/or off-response enhancement in almost half the investigated 122 neurons favors not only perception of single calls but also of vocalization rhythm. In summary, our study provides strong evidence that critical-band resolved frequency components within a communication sound increase the probability of its perception by boosting the signal-to-noise ratio of neural response rates within the inferior colliculus for at least 20% (our criterion for facilitation). These mechanisms, including enhancement of rhythm coding, are generally favorable to processing of other animal and human vocalizations, including formants of speech sounds.

Connectional Modularity of Top-Down and Bottom-Up Multimodal Inputs to the Lateral Cortex of the Mouse Inferior Colliculus.

Many brain regions contain subnuclear microarchitectures, such as the matrix-striosome organization of the basal ganglia or the patch-interpatch organization of the visual cortex, that shed light on circuit complexities. In the present study, we demonstrate the presence of one such micro-organization in the rodent inferior colliculus. While this structure is typically viewed as an auditory integration center, its lateral cortex appears to be involved in multisensory operations and receives input from somatosensory brain regions. We show here that the lateral cortex can be further subdivided into multiple processing streams: modular regions, which are targeted by somatosensory inputs, and extramodular zones that receive auditory information.

Passive stimulation and behavioral training differentially transform temporal processing in the inferior colliculus and primary auditory cortex.

Behaviorally relevant vs. passive electric stimulation of the auditory nerve differentially affects neuronal temporal processing in the central nucleus of the inferior colliculus (ICC) and the primary auditory cortex (AI) in profoundly short-deaf and long-deaf cats. Temporal plasticity in the ICC depends on a critical amount of electric stimulation, independent of its behavioral relevance. In contrast, the AI emerges as a pivotal site for behaviorally driven neuronal temporal plasticity in the deaf auditory system.

Slow Temporal Integration Enables Robust Neural Coding and Perception of a Cue to Sound Source Location.

In mammals, localization of sound sources in azimuth depends on sensitivity to interaural differences in sound timing (ITD) and level (ILD). Paradoxically, while typical ILD-sensitive neurons of the auditory brainstem require millisecond synchrony of excitatory and inhibitory inputs for the encoding of ILDs, human and animal behavioral ILD sensitivity is robust to temporal stimulus degradations (e.g., interaural decorrelation due to reverberation), or, in humans, bilateral clinical device processing. Here we demonstrate that behavioral ILD sensitivity is only modestly degraded with even complete decorrelation of left- and right-ear signals, suggesting the existence of a highly integrative ILD-coding mechanism. Correspondingly, we find that a majority of auditory midbrain neurons in the central nucleus of the inferior colliculus (of chinchilla) effectively encode ILDs despite complete decorrelation of left- and right-ear signals. We show that such responses can be accounted for by relatively long windows of bilateral excitatory-inhibitory interaction, which we explicitly measure using trains of narrowband clicks. Neural and behavioral data are compared with the outputs of a simple model of ILD processing with a single free parameter, the duration of excitatory-inhibitory interaction. Behavioral, neural, and modeling data collectively suggest that ILD sensitivity depends on binaural integration of excitation and inhibition within a ≳3 ms temporal window, significantly longer than observed in lower brainstem neurons. This relatively slow integration potentiates a unique role for the ILD system in spatial hearing that may be of particular importance when informative ITD cues are unavailable. In mammalian hearing, interaural differences in the timing (ITD) and level (ILD) of impinging sounds carry critical information about source location. However, natural sounds are often decorrelated between the ears by reverberation and background noise, degrading the fidelity of both ITD and ILD cues. Here we demonstrate that behavioral ILD sensitivity (in humans) and neural ILD sensitivity (in single neurons of the chinchilla auditory midbrain) remain robust under stimulus conditions that render ITD cues undetectable. This result can be explained by "slow" temporal integration arising from several-millisecond-long windows of excitatory-inhibitory interaction evident in midbrain, but not brainstem, neurons. Such integrative coding can account for the preservation of ILD sensitivity despite even extreme temporal degradations in ecological acoustic stimuli.

L-type calcium channels refine the neural population code of sound level.

The coding of sound level by ensembles of neurons improves the accuracy with which listeners identify how loud a sound is. In the auditory system, the rate at which neurons fire in response to changes in sound level is shaped by local networks. Voltage-gated conductances alter local output by regulating neuronal firing, but their role in modulating responses to sound level is unclear. We tested the effects of L-type calcium channels (CaL: CaV1.1-1.4) on sound-level coding in the central nucleus of the inferior colliculus (ICC) in the auditory midbrain. We characterized the contribution of CaL to the total calcium current in brain slices and then examined its effects on rate-level functions (RLFs) in vivo using single-unit recordings in awake mice. CaL is a high-threshold current and comprises ∼50% of the total calcium current in ICC neurons. In vivo, CaL activates at sound levels that evoke high firing rates. In RLFs that increase monotonically with sound level, CaL boosts spike rates at high sound levels and increases the maximum firing rate achieved. In different populations of RLFs that change nonmonotonically with sound level, CaL either suppresses or enhances firing at sound levels that evoke maximum firing. CaL multiplies the gain of monotonic RLFs with dynamic range and divides the gain of nonmonotonic RLFs with the width of the RLF. These results suggest that a single broad class of calcium channels activates enhancing and suppressing local circuits to regulate the sensitivity of neuronal populations to sound level.

The contribution of inferior colliculus activity to the auditory brainstem response (ABR) in mice

In mice, the auditory brainstem response (ABR) is frequently used to assess hearing status in transgenic hearing models. The diagnostic value of the ABR depends on knowledge about the anatomical sources of its characteristic waves. Here, we studied the contribution of the inferior colliculus (IC) to the click-evoked scalp ABR in mice. We demonstrate a non-invasive correlate of the IC response that can be measured in the scalp ABR as a slow positive wave P0 with peak latency 7–8 ms when recorded with adequate band-pass filtering. Wave P0 showed close correspondence in latency, magnitude and shape with the sustained part of evoked spiking activity and local field potentials (LFP) in the central nucleus of the IC. In addition, the onset peaks of the IC response were related temporally to ABR wave V and to some extent to wave IV. This relation was further supported by depth-dependent modulation of the shape of ABR wave IV and V within the IC suggesting generation within or in close vicinity to the IC. In conclusion, the slow ABR wave P0 in the scalp ABR may represent a complementary non-invasive marker for IC activity in the mouse. Further, the latency of synchronized click-evoked activity in the IC supports the view that IC contributes to ABR wave V, and possibly also to ABR wave IV.

Synchrony, connectivity, and functional similarity in auditory midbrain local circuits

The central nucleus of the inferior colliculus (ICC) contains a laminar structure that functions as an organizing substrate of ascending inputs and local processing. While topographic distributions of ICC response parameters within and across laminae have been reported, the functional micro-organization of the ICC is less well understood. For pairs of neighboring ICC neurons, we examined the nature of functional connectivity and receptive field preferences to gain a better understanding of the structure and function of local circuits. By recording from pairs of adjacent neurons and presenting pure-tone and dynamic broad-band stimulation, we estimated functional connectivity and local differences in frequency response areas (FRAs), spectrotemporal receptive fields (STRFs), nonlinear input/output functions, and single-spike information. From the cross-covariance functions we identified putative unidirectional as well as bidirectional excitatory/inhibitory interactions. STRFs of neighboring neurons strongly conserve best frequency, and moderately agree in STRF similarity, bandwidth, temporal response type, best modulation frequency, nonlinearity structure, and degree of information processing. Excitatory connectivity was stronger and temporally more precise than for inhibitory connections. Neither connection strength nor degree of synchrony correlated with receptive field parameters. The functional similarity of local pairs of ICC neurons was substantially less than for local pairs in the granular layers of primary auditory cortex (AI). These results imply that while the ICC is an obligatory nexus of ascending information, local neurons are comparatively weakly connected and exhibit considerable receptive field variability, potentially reflecting the heterogeneity of converging inputs to ICC functional zones.

Enhancement of forward suppression begins in the ventral cochlear nucleus

A neuron׳s response to a sound can be suppressed by the presentation of a preceding sound. It has been suggested that this suppression is a direct correlate of the psychophysical phenomenon of forward masking, however, forward suppression, as measured in the responses of the auditory nerve, was insufficient to account for behavioural performance. In contrast the neural suppression seen in the inferior colliculus and auditory cortex was much closer to psychophysical performance. In anaesthetised guinea-pigs, using a physiological two-interval forced-choice threshold tracking algorithm to estimate suppressed (masked) thresholds, we examine whether the enhancement of suppression can occur at an earlier stage of the auditory pathway, the ventral cochlear nucleus (VCN). We also compare these responses with the responses from the central nucleus of the inferior colliculus (ICc) using the same preparation. In both nuclei, onset-type neurons showed the greatest amounts of suppression (16.9–33.5dB) and, in the VCN, these recovered with the fastest time constants (14.1–19.9ms). Neurons with sustained discharge demonstrated reduced masking (8.9–12.1dB) and recovery time constants of 27.2–55.6ms. In the VCN the decrease in growth of suppression with increasing suppressor level was largest for chopper units and smallest for onset-type units. The threshold elevations recorded for most unit types are insufficient to account for the magnitude of forward masking as measured behaviourally, however, onset responders, in both the cochlear nucleus and inferior colliculus demonstrate a wide dynamic range of suppression, similar to that observed in human psychophysics.

Graded and discontinuous EphA–ephrinB expression patterns in the developing auditory brainstem

Eph–ephrin interactions guide topographic mapping and pattern formation in a variety of systems. In contrast to other sensory pathways, their precise role in the assembly of central auditory circuits remains poorly understood. The auditory midbrain, or inferior colliculus (IC) is an intriguing structure for exploring guidance of patterned projections as adjacent subdivisions exhibit distinct organizational features. The central nucleus of the IC (CNIC) and deep aspects of its neighboring lateral cortex (LCIC, Layer 3) are tonotopically-organized and receive layered inputs from primarily downstream auditory sources. While less is known about more superficial aspects of the LCIC, its inputs are multimodal, lack a clear tonotopic order, and appear discontinuous, terminating in modular, patch/matrix-like distributions. Here we utilize X-Gal staining approaches in lacZ mutant mice (ephrin-B2, -B3, and EphA4) to reveal EphA–ephrinB expression patterns in the nascent IC during the period of projection shaping that precedes hearing onset. We also report early postnatal protein expression in the cochlear nuclei, the superior olivary complex, the nuclei of the lateral lemniscus, and relevant midline structures. Continuous ephrin-B2 and EphA4 expression gradients exist along frequency axes of the CNIC and LCIC Layer 3. In contrast, more superficial LCIC localization is not graded, but confined to a series of discrete ephrin-B2 and EphA4-positive Layer 2 modules. While heavily expressed in the midline, much of the auditory brainstem is devoid of ephrin-B3, including the CNIC, LCIC Layer 2 modular fields, the dorsal nucleus of the lateral lemniscus (DNLL), as well as much of the superior olivary complex and cochlear nuclei. Ephrin-B3 LCIC expression appears complementary to that of ephrin-B2 and EphA4, with protein most concentrated in presumptive extramodular zones. Described tonotopic gradients and seemingly complementary modular/extramodular patterns suggest Eph–ephrin guidance in establishing juxtaposed continuous and discrete neural maps in the developing IC prior to experience.

Long-Lasting Sound-Evoked Afterdischarge in the Auditory Midbrain.

Different forms of plasticity are known to play a critical role in the processing of information about sound. Here, we report a novel neural plastic response in the inferior colliculus, an auditory center in the midbrain of the auditory pathway. A vigorous, long-lasting sound-evoked afterdischarge (LSA) is seen in a subpopulation of both glutamatergic and GABAergic neurons in the central nucleus of the inferior colliculus of normal hearing mice. These neurons were identified with single unit recordings and optogenetics in vivo. The LSA can continue for up to several minutes after the offset of the sound. LSA is induced by long-lasting, or repetitive short-duration, innocuous sounds. Neurons with LSA showed less adaptation than the neurons without LSA. The mechanisms that cause this neural behavior are unknown but may be a function of intrinsic mechanisms or the microcircuitry of the inferior colliculus. Since LSA produces long-lasting firing in the absence of sound, it may be relevant to temporary or chronic tinnitus or to some other aftereffect of long-duration sound.

Emergence of Spatial Stream Segregation in the Ascending Auditory Pathway.

Listeners are capable of disentangling multiple competing sequences of sounds that originate from distinct sources. This stream segregation is aided by differences in spatial location between the sources. A possible substrate of spatial stream segregation (SSS) has been described in the auditory cortex, but the mechanisms leading to those cortical responses are unknown. Here, we investigated SSS in three levels of the ascending auditory pathway with extracellular unit recordings in anesthetized rats. We found that neural SSS emerges within the ascending auditory pathway as a consequence of sharpening of spatial sensitivity and increasing forward suppression. Our results highlight brainstem mechanisms that culminate in SSS at the level of the auditory cortex.

Effects of Stimulation of the Inferior Colliculi in Krushinskii–Molodkina Rats

The effects of chemical and electrical stimulation of the central nucleus of the inferior colliculus on the generation and formation of convulsive manifestations and on the organization of sleep were studied in Krushinskii–Molodkina rats with an inherited predisposition to audiogenic convulsions. Microinjection of quinolinic acid (10 μg in 1 μl of distilled water) or electrical stimulation at a frequency of 70 Hz generated paroxysmal manifestations in the form of intense rotatory movement acts, similar to “wild running” of animals in the initial convulsion-free stage of audiogenic seizures. This provides grounds for suggesting that in Krushinskii–Molodkina rats the inferior colliculi are part of the neural network responsible for the generation and execution of the running stage during the formation of convulsive responses to sound stimuli. Application of these stimuli was also followed by a decrease in the total duration of fast-wave sleep during the poststimulus period. Conversely, electrical stimulation of the inferior colliculi at a frequency of 7 Hz on the background of deep slow-wave sleep induced episodes of fast-wave sleep in the rats; after 3–4 sessions of this stimulation producing this effect, there was an almost two-fold increase in the total duration of fastwave sleep during the post-stimulus period due to an increase in the number but not the duration of these episodes. These results provide evidence that the inferior colliculi in rats may have a modulatory effect on the functioning of the fast-wave sleep triggering system.

Cooling of the auditory cortex modifies neuronal activity in the inferior colliculus in rats

There are powerful pathways descending from the auditory cortex (AC) to the inferior colliculus (IC), yet their function is not fully understood. The aim of this study is to examine the effects of a reversible cortical inactivation, achieved by cooling of the AC, on the responses of neurons in the rat IC. Extracellular single-unit or multi-unit activity was recorded in the IC of anaesthetized rats with a 16-channel multielectrode probe introduced along the IC dorso-ventral axis through the dorsal cortex (DCIC) to the central nucleus of the IC (CIC). Cooling of the AC produced an increase in spontaneous activity and magnitude of the sound-evoked response in 47% of the IC neurons. Maximal changes in the neuronal activity were observed in the DCIC and the central part of the CIC. The final segments of the sustained responses to 60 ms stimuli and the off responses were more affected than the onset segments. Inactivation of the AC resulted in a suppression of the post-excitatory inhibition and neuronal adaptation, which was reflected in a pronounced enhancement of synchronized responses to a series of fast repeated clicks. The response parameters recovered, at least partly, to the pre-cooling levels 1 h after the cooling cessation. The frequency tuning properties of the IC neurons did not show any significant changes during the cooling period. The results demonstrate that AC cooling inactivates excitatory corticofugal pathways and results in a less activated intrinsic inhibitory network in the IC.

Thin-film micro-electrode stimulation of the cochlea in rats exposed to aminoglycoside induced hearing loss

The multi-channel cochlear implant (CI) provides sound and speech perception to thousands of individuals who would otherwise be deaf. Broad activation of auditory nerve fibres when using a CI results in poor frequency discrimination. The CI also provides users with poor amplitude perception due to elicitation of a narrow dynamic range. Provision of more discrete frequency perception and a greater control over amplitude may allow users to better distinguish speech in noise and to segregate sound sources. In this research, thin-film (TF) high density micro-electrode arrays and conventional platinum ring electrode arrays were used to stimulate the cochlea of rats administered sensorineural hearing loss (SNHL) via ototoxic insult, with neural responses taken at 434 multiunit clusters in the central nucleus of the inferior colliculus (CIC). Threshold, dynamic range and broadness of response were used to compare electrode arrays. A stronger current was required to elicit CIC threshold when using the TF array compared to the platinum ring electrode array. TF stimulation also elicited a narrower dynamic range than the PR counterpart. However, monopolar stimulation using the TF array produced more localised CIC responses than other stimulation strategies. These results suggest that individuals with SNHL could benefit from micro stimulation of the cochlea using a monopolar configuration which may provide discrete frequency perception when using TF electrode arrays.

Neurophysiological approaches to studying the functional role of auditory critical bands

Neurophysiological data on the evaluation of neural correlates of the involvement of auditory critical bands in sound localization and recognition are presented. Single unit activity was recorded extracellularly in the central nucleus of the inferior colliculus in house mouse females. In the first part, the neuronal sensitivity to acoustic signals simulating spectral localization cues (notch noise with different bandwidths) was studied. Evaluation of neuronal response variability depending on notch bandwidths revealed that the 1/3 octave notch bandwidth was optimal for the analysis of the localization-significant spectral information. This notch bandwidth corresponded to the average critical bandwidth of the auditory midbrain neurons determined previously by the narrow-band masking method. In the second part, the selectivity of neuronal responses to a discomfort-signaling mouse pup wriggling call, its models and frequency components, was evaluated. The data obtained demonstrated that the wriggling call models with frequency components located, like in a natural call, in three non-overlapping critical bands evoked stronger neuronal responses than the other models. These findings support the suggestion of the universal role the critical-band mechanism plays in processing different parameters of acoustic stimuli.

Auditory midbrain processing is differentially modulated by auditory and visual cortices: An auditory fMRI study

The cortex contains extensive descending projections, yet the impact of cortical input on brainstem processing remains poorly understood. In the central auditory system, the auditory cortex contains direct and indirect pathways (via brainstem cholinergic cells) to nuclei of the auditory midbrain, called the inferior colliculus (IC). While these projections modulate auditory processing throughout the IC, single neuron recordings have samples from only a small fraction of cells during stimulation of the corticofugal pathway. Furthermore, assessments of cortical feedback have not been extended to sensory modalities other than audition. To address these issues, we devised blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) paradigms to measure the sound-evoked responses throughout the rat IC and investigated the effects of bilateral ablation of either auditory or visual cortices. Auditory cortex ablation increased the gain of IC responses to noise stimuli (primarily in the central nucleus of the IC) and decreased response selectivity to forward species-specific vocalizations (versus temporally reversed ones, most prominently in the external cortex of the IC). In contrast, visual cortex ablation decreased the gain and induced a much smaller effect on response selectivity. The results suggest that auditory cortical projections normally exert a large-scale and net suppressive influence on specific IC subnuclei, while visual cortical projections provide a facilitatory influence. Meanwhile, auditory cortical projections enhance the midbrain response selectivity to species-specific vocalizations. We also probed the role of the indirect cholinergic projections in the auditory system in the descending modulation process by pharmacologically blocking muscarinic cholinergic receptors. This manipulation did not affect the gain of IC responses but significantly reduced the response selectivity to vocalizations. The results imply that auditory cortical gain modulation is mediated primarily through direct projections and they point to future investigations of the differential roles of the direct and indirect projections in corticofugal modulation. In summary, our imaging findings demonstrate the large-scale descending influences, from both the auditory and visual cortices, on sound processing in different IC subdivisions. They can guide future studies on the coordinated activity across multiple regions of the auditory network, and its dysfunctions.