Central Nucleus Of Inferior Colliculus Research Articles

Long-Duration Sound-Induced Facilitation Changes Population Activity in the Inferior Colliculus.

The inferior colliculus (IC) is at the midpoint of the auditory system and integrates virtually all information ascending from the auditory brainstem, organizes it, and transmits the results to the auditory forebrain. Its abundant, excitatory local connections are crucial for this task. This study describes a long duration sound (LDS)-induced potentiation in the IC that changes both subsequent tone-evoked responses and spontaneous activity. Afterdischarges, changes of spontaneous spiking following an LDS, were seen previously in single neurons. Here, we used multi-channel probes to record activity before and after a single, tetanic sound and describe the changes in a population of IC neurons. Following a 60 s narrowband-noise stimulation, a subset of recording channels (∼16%) showed afterdischarges. A facilitated response spike rate to tone pips following an LDS was also observed in ∼16% of channels. Both channels with an afterdischarge and channels with facilitated tone responses had higher firing rates in response to LDS, and the magnitude of the afterdischarges increased with increased responses to the LDS. This is the first study examining the effect of LDS stimulation on tone-evoked responses. This observed facilitation in vivo has similarities to post-tetanic potentiation in vitro as both manner of induction (strong stimulation for several seconds) as well as time-course of the facilitation (second to minute range) are comparable. Channels with and without facilitation appear to be intermixed and distributed widely in the central nucleus of IC, and this suggests a heretofore unknown property of some IC neurons or their circuits. Consequently, this sound-evoked facilitation may enhance the sound-evoked output of these neurons, while, simultaneously, most other IC neurons have reduced or unchanged output in response to the same stimulus.

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.

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.

General anesthetic induced differential changes in latency of auditory evoked potential in the central nucleus of inferior colliculus of mouse

Confirming the effect of general anesthetic on brainstem auditory evoked potential (BAEP) is important to interpret BAEP data, elucidate the neuroanatomical sites of action of general anesthetic and monitor the effect of general anesthetic. However, the effect of general anesthetic on BAEP is not thoroughly understood, which may be due to unreasonable acoustic stimulation scheme. This study aimed to redesign acoustic stimulation scheme and attempted to test our hypothesis that general anesthetic induces differential changes in BAEP latency in mouse. Auditory evoked potential in the central nucleus of inferior colliculus (AEP-ICC) was used to represent BAEP. Every 10 min after pentobarbital anesthesia, AEP-ICC was recorded by delivering tones with a rate of 1/s, and pentobarbital blood concentration (PBC) was measured, until the mice awoke. AEP-ICC latency to 80-dB SPL sounds (L80) and latency change in nerve fibers (ΔL) did not present regular changes, and AEP-ICC latency to 50-dB SPL sounds (L50) and latency change in synapses (ΔI) gradually decreased as pentobarbital was metabolized. L50 and ΔI changes were exponentially associated with decreased PBC, and L50 showed a linear relationship with ΔI. We conclude that, general anesthetic acts on auditory brainstem; general anesthetic does not alter L80 and ΔL but increases L50 and ΔI; L80 and ΔL can evaluate the function of auditory brainstem and its inferior structures under general anesthesia; L50 and ΔI exponentially reflect the blood concentration of a general anesthetic.

Apoptosis and proliferation in the inferior colliculus during postnatal development and epileptogenesis in audiogenic Krushinsky–Molodkina rats

It is known that audiogenic seizure (AGS) expression is based on the activation of the midbrain structures such as the inferior colliculus (IC). It was demonstrated that excessive sound exposure during the postnatal developments of the IC in rats led to AGS susceptibility in adulthood, which correlated with underdevelopment of the IC. In adult rodents, noise overstimulation induced apoptosis in the IC. The purpose of this study was to investigate postnatal development of the IC in rats genetically prone to AGS and to check if audiogenic kindling would activate apoptosis and/or proliferation in the IC. In our study, we used inbred audiogenic Krushinsky–Molodkina (KM) rats, which are characterized by age-dependent seizure expression. Analysis of postnatal development showed the increased number of proliferating cells in the IC central nucleus of KM rats on the 14th postnatal day (P14) in comparison with those of Wistar rats. Moreover, we also observed increased apoptosis level and decreased general cell population in the IC central nucleus. These data pointed towards a delayed development of the IC in KM rats. Analysis of the IC central nucleus of KM rat after audiogenic kindling for a week, with one AGS per day, demonstrated dramatically increased cell death, which was accompanied with a reduction of general cell population. Audiogenic kindling also decreased proliferation in the IC central nucleus. However, a week after the last AGS, the number of proliferating cells was increased, which supposes a certain compensatory mechanism to prevent cell loss.

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.

The organization of frequency and binaural cues in the gerbil inferior colliculus.

The inferior colliculus (IC) is the common target of separate pathways that transmit different types of auditory information. Beyond tonotopy, little is known about the organization of response properties within the 3-dimensional layout of the auditory midbrain in most species. Through study of interaural time difference (ITD) processing, the functional properties of neurons can be readily characterized and related to specific pathways. To characterize the representation of ITDs relative to the frequency and hodological organization of the IC, the properties of neurons were recorded and the sites recovered histologically. Subdivisions of the IC were identified based on cytochrome oxidase (CO) histochemistry. The results were plotted within a framework formed by an MRI atlas of the gerbil brain. The central nucleus was composed of two parts, and lateral and dorsal cortical areas were identified. The lateral part of the central nucleus had the highest CO activity in the IC and a high proportion of neurons sensitive to ITDs. The medial portion had lower CO activity and fewer ITD-sensitive neurons. A common tonotopy with a dorsolateral to ventromedial gradient of low to high frequencies spanned the two regions. The distribution of physiological responses was in close agreement with known patterns of ascending inputs. An understanding of the 3-dimensional organization of the IC is needed to specify how the single tonotopic representation in the IC central nucleus leads to the multiple tonotopic representations in core areas of the auditory cortex.

Audiogenic seizure activity following HSV-1 GAD65 sense or antisense injection into inferior colliculus of Long-Evans rat.

Herpes virus technology involving manipulation of GAD65 was used to study effects on audiogenic seizures (AGS). Audiogenic seizure behaviors were examined following injections of replication-defective herpes simplex virus (HSV-1) vectors incorporating sense or antisense toward GAD65 along with 10% lac-Z into the central nucleus of inferior colliculus (CNIC) of Long-Evans rats. In seizure-sensitive animals developmentally primed by intense sound exposure, injection of GAD65 in the sense orientation increased wild running latencies and reduced incidence of clonus compared with lac-Z only, unoperated, and vehicle seizure groups. In contrast, infection of CNIC with GAD65 antisense virus resulted in 100% incidence of wild running and clonus behaviors in AGS animals. Unprimed animals not operated continued to show uniform absence of seizure activity. Administration of GAD65 antisense virus into CNIC produced novel wild running and clonus behaviors in some unprimed animals. Staining for β-galactosidase in all vector animals revealed no differences in pattern or numbers of immunoreactive cells at injection sites. Qualitatively, typical small and medium multipolar/stellate and medium fusiform neurons appeared in the CNIC of vector animals. These results demonstrate that HSV-1 vector constructs implanted into the CNIC can predictably influence incidence and severity of AGS and suggest that viral vectors can be useful in studying GABA mechanisms with potential for therapeutic application in epilepsy. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

The time scale of adaptation in tonal sequence processing by the mouse auditory midbrain neurons.

The time course of poststimulatory adaptation of the inferior colliculus central nucleus (ICC) of CBB6F1 hybrid mice to sound sequences, specifically, series of four tonal stimuli presented at intervals of 0, 2, 4, 10, 20, 50, 100, 200, 500, 700, 1000, and 1500 ms were studied. Assessment of the adaptation of the entire neuronal population have shown that, at an interstimulus interval of 0-200 ms, the response to the first tone in a series is significantly stronger than those to the second to fourth tones, the strengths of the latter three responses not differing significantly from one another. If the interstimulus interval is 500 ms or longer, the response to none of the tones in a series differs significantly in strength from the others. The role of adaptation of midbrain neurons to the grouping of components of bioacoustic stimuli is discussed.

Development of intrinsic connectivity in the central nucleus of the mouse inferior colliculus.

The inferior colliculus (IC) in the mammalian midbrain is the major subcortical auditory integration center receiving ascending inputs from almost all auditory brainstem nuclei as well as descending inputs from the thalamus and cortex. In addition to these extrinsic inputs, the IC also contains a dense network of local, intracollicular connections, which are thought to provide gain control and contribute to the selectivity for complex acoustic features. However, in contrast to the organization of extrinsic IC afferents, the development and functional organization of intrinsic connections in the IC has remained poorly understood. Here we used laser-scanning photostimulation with caged glutamate to characterize the spatial distribution and strength of local synaptic connections in the central nucleus of the inferior colliculus of newborn mice until after hearing onset (P2-P22). We demonstrate the presence of an extensive excitatory and inhibitory intracollicular network already at P2. Excitatory and inhibitory synaptic maps to individual IC neurons formed continuous maps that largely overlapped with each other and that were aligned with the presumed isofrequency axis of the central nucleus of the IC. Although this characteristic organization was present throughout the first three postnatal weeks, the size of input maps was developmentally regulated as input maps underwent an expansion during the first week that was followed by a dramatic refinement after hearing onset. These changes occurred in parallel for excitatory and inhibitory input maps. However, the functional elimination of intrinsic connections was greater for excitatory than for inhibitory connections, resulting in a predominance of intrinsic inhibition after hearing onset.

Excitatory and inhibitory projections in parallel pathways from the inferior colliculus to the auditory thalamus.

Individual subdivisions of the medial geniculate body (MG) receive a majority of their ascending inputs from 1 or 2 subdivisions of the inferior colliculus (IC). This establishes parallel pathways that provide a model for understanding auditory projections from the IC through the MG and on to auditory cortex. A striking discovery about the tectothalamic circuit was identification of a substantial GABAergic component. Whether GABAergic projections match the parallel pathway organization has not been examined. We asked whether the parallel pathway concept is reflected in guinea pig tectothalamic pathways and to what degree GABAergic cells contribute to each pathway. We deposited retrograde tracers into individual MG subdivisions (ventral, MGv; medial, MGm; dorsal, MGd; suprageniculate, MGsg) to label tectothalamic cells and used immunochemistry to identify GABAergic cells. The MGv receives most of its IC input (~75%) from the IC central nucleus (ICc); MGd and MGsg receive most of their input (~70%) from IC dorsal cortex (ICd); and MGm receives substantial input from both ICc (~40%) and IC lateral cortex (~40%). Each MG subdivision receives additional input (up to 32%) from non-dominant IC subdivisions, suggesting cross-talk between the pathways. The proportion of GABAergic cells in each pathway depended on the MG subdivision. GABAergic cells formed ~20% of IC inputs to MGv or MGm, ~11% of inputs to MGd, and 4% of inputs to MGsg. Thus, non-GABAergic (i.e., glutamatergic) cells are most numerous in each pathway with GABAergic cells contributing to different extents. Despite smaller numbers of GABAergic cells, their distributions across IC subdivisions mimicked the parallel pathways. Projections outside the dominant pathways suggest opportunities for excitatory and inhibitory crosstalk. The results demonstrate parallel tectothalamic pathways in guinea pigs and suggest numerous opportunities for excitatory and inhibitory interactions within and between pathways.

Excitatory and inhibitory tonotopic bands in chinchilla inferior colliculus revealed by c-fos immuno-labeling

We describe in detail a reliable experimental protocol for c-fos immuno-labeling of patterns of neural activation in the chinchilla (chinchilla laniger). We report on resting-level neural activity in inferior colliculus (IC) of auditory midbrain, and on tonotopic bands present following 90 min of pure-tone sound stimulation. Neurons activated by 6-kHz sound stimulation lay ventro-medial to those activated at 2 kHz. This is consistent with the known tonotopic organization of IC, and verified in the present report by multi-unit neuron response recordings in central nucleus of IC. Of particular interest, we observe a significant reduction in cell labeling adjacent to the tonotopic bands, and suggest that such decreases represent inhibitory regions. C-fos-labeled bands and lateral regions of reduced labeling resemble excitatory and lateral-inhibitory response areas of IC neurons.

Neuronal interaural level difference response shifts are level-dependent in the rat auditory cortex

How does the brain accomplish sound localization with invariance to total sound level? Sensitivity to interaural level differences (ILDs) is first computed at the lateral superior olive (LSO) and is observed at multiple levels of the auditory pathway, including the central nucleus of inferior colliculus (ICC) and auditory cortex. In LSO, this ILD sensitivity is level-dependent, such that ILD response functions shift toward the ipsilateral (excitatory) ear with increasing sound level. Thus early in the processing pathway changes in firing rate could indicate changes in sound location, sound level, or both. In ICC, while ILD responses can shift toward either ear in individual neurons, there is no net ILD response shift at the population level. In behavioral studies of human sound localization acuity, ILD sensitivity is invariant to increasing sound levels. Level-invariant sound localization would suggest transformation in level sensitivity between LSO and perception of sound sources. Whether this transformation is completed at the level of the ICC or continued at higher levels remains unclear. It also remains unknown whether perceptual sound localization is level-invariant in rats, as it is in humans. We asked whether ILD sensitivity is level-invariant in rat auditory cortex. We performed single-unit and whole cell recordings in rat auditory cortex under ketamine anesthesia and measured responses to white noise bursts presented through sealed earphones at a range of ILDs. Surprisingly, we found that with increasing sound levels ILD responses shifted toward the ipsilateral ear (which is typically inhibitory), regardless of whether cells preferred ipsilateral, contralateral, or binaural stimuli. Voltage-clamp recordings suggest that synaptic inhibition does not contribute substantially to this transformation in level sensitivity. We conclude that the level invariance of ILD sensitivity seen in behavioral studies is not present in rat auditory cortex.

Interaural Level Difference-Dependent Gain Control and Synaptic Scaling Underlying Binaural Computation

Binaural integration in the central nucleus of inferior colliculus (ICC) plays a critical role in sound localization. However, its arithmetic nature and underlying synaptic mechanisms remain unclear. Here, we showed in mouse ICC neurons that the contralateral dominance is created by a "push-pull"-like mechanism, with contralaterally dominant excitation and more bilaterally balanced inhibition. Importantly, binaural spiking response is generated apparently from an ipsilaterally mediated scaling of contralateral response, leaving frequency tuning unchanged. This scaling effect is attributed to a divisive attenuation ofcontralaterally evoked synaptic excitation onto ICC neurons with their inhibition largely unaffected. Thus, a gain control mediates the linear transformation from monaural to binaural spike responses. The gain value is modulated by interaural level difference (ILD) primarily through scaling excitation to different levels. The ILD-dependent synaptic scaling and gain adjustment allow ICC neurons to dynamically encode interaural sound localization cues while maintaining an invariant representation of other independent sound attributes.

Experience-dependent overrepresentation of ultrasonic vocalization frequencies in the rat primary auditory cortex

Cortical sensory representation is highly adaptive to the environment, and prevalent or behaviorally important stimuli are often overrepresented. One class of such stimuli is species-specific vocalizations. Rats vocalize in the ultrasonic range >30 kHz, but cortical representation of this frequency range has not been systematically examined. We recorded in vivo cortical electrophysiological responses to ultrasonic pure-tone pips, natural ultrasonic vocalizations, and pitch-shifted vocalizations to assess how rats represent this ethologically relevant frequency range. We find that nearly 40% of the primary auditory cortex (AI) represents an octave-wide band of ultrasonic vocalization frequencies (UVFs; 32-64 kHz) compared with <20% for other octave bands <32 kHz. These UVF neurons respond preferentially and reliably to ultrasonic vocalizations. The UVF overrepresentation matures in the cortex before it develops in the central nucleus of inferior colliculus, suggesting a cortical origin and corticofugal influences. Furthermore, the development of cortical UVF overrepresentation depends on early acoustic experience. These results indicate that natural sensory experience causes large-scale cortical map reorganization and improves representations of species-specific vocalizations.

Repeated exposure to a tone transiently alters spectral tuning bandwidth of neurons in the central nucleus of inferior colliculus in juvenile rats

Early acoustic experience changes tonal frequency tuning in the inferior colliculus (IC) and the primary auditory cortex. The contributions of IC plasticity to cortical frequency map reorganization are not entirely clear. While most cortical plasticity studies exposed animals to pulsed tones, studies of IC plasticity used either noise or a continuous tone. Here we compared the effects of repeated exposure to single-frequency tone pips on cortical and IC frequency representations in juvenile rats. We found that while tone exposure caused a long-lasting increase in cortical representations of the exposure frequency, changes to IC neurons were limited to a transient narrowing of tuning bandwidth. These results suggest that previously documented cortical frequency map reorganization does not depend on similar changes in the subcortical auditory nuclei.

Combination-sensitive neurons in the central nucleus of inferior colliculus of the house mouse Mus musculus

tion in this analysis. The goal of the present work was to reveal mechanisms of spectral processing of complex communicative signals by neurons of the central nucleus of inferior colliculus.This work evaluates extracellular activity of single neurons of the central nucleus of the house mouse inferior colliculus, evoked by call of dis-comfort from repertoire of early ontogeny of the mouse pups, so called “wriggling call,” its model reproducing harmonic structure of natural call and its frequency components. The wriggling call is a nest call of discomfort of mouse pups. It in-duces the instinctive maternal behavior—care of pups, building of nest, and a change of the mater-nal body position during lactation [7]. The main features of the call are its low frequency range (the main energy is concentrated between 2 and 15 kHz) and the pronounced harmonic structure (the call is formed by three major equally-powered harmonics located at 5, 10, and 15 kHz). Neu-ral responses to the wriggling call model, natural wriggling call, and its components were compared with organization of neuronal frequency receptive fields.The study was carried out on females of F1 hy-brids of CBA and C57BL/6 strains at the age of 8–15 weeks. Anesthesia was performed by intra-The most important function of the auditory system is processing of communicative acoustic signals. However, how analysis of communica-tive signals occurs in the brain auditory centers re-mains to be elucidated and, moreover, we do not know what principles underlie the communicative signal discrimination by the auditory system from the diversity of complex sounds. Studies of neuro-nal mechanisms of the analysis of species-specific signals were carried out predominantly in the fore-brain auditory centers of the acoustically special-ized objects [1–3]. At the same time, numerous ascending, descending, and commissural connec-tions of neurons of the midbrain auditory center, the inferior colliculus, structural orderliness of its central nucleus, location of information about var-ious features of auditory signals, high variability of neuronal response patterns allow suggesting that this structure has necessary prerequisites for en-coding of communicative signals [4]. However, so far, there are only occasional works showing selec-tivity of neuronal responses in the central nucleus of the bat inferior colliculus to species-specific signals [5, 6], while neurophysiologic mechanisms of analysis of communicative signals at the level of midbrain auditory neurons remain practically not studied. Much less studied is neuronal specializa-

EphA4 and ephrin‐B2 expression patterns during inferior colliculus projection shaping prior to experience

Central processing of complex auditory tasks requires elaborate circuitry. The auditory midbrain, or inferior colliculus (IC), epitomizes such precise organization, where converging inputs form discrete, tonotopically-arranged axonal layers. Previously in rat, we established that shaping of multiple afferent patterns in the IC central nucleus (CNIC) occurs prior to experience. This study implicates an Eph receptor tyrosine kinase and a corresponding ephrin ligand in signaling this early topographic registry. We report that EphA4 and ephrin-B2 expression patterns in the neonatal rat and mouse IC correlate temporally and spatially with that of developing axonal layers. DiI-labeling confirms projections arising from the lateral superior olive (LSO) form frequency-specific layers within the ipsilateral and contralateral mouse CNIC, as has been described in other species. Immunohistochemistry (EphA4 and ephrin-B2) and ephrin-B2 lacZ histochemistry reveal clear gradients in expression across the tonotopic axis, with most concentrated labeling observed in high-frequency, ventromedial aspects of the CNIC. Discrete patches of labeling were also discernible in the external cortex of the IC (ECIC; EphA4 patches in rat, ephrin-B2 patches in mouse). Observed gradients in the CNIC and compartmentalized ECIC expression persisted through the first postnatal week, before becoming less intense and more homogeneously distributed by the functional onset of hearing. EphA4 and ephrin-B2-positive neurons were evident in several auditory brainstem nuclei known to send patterened inputs to the IC. These findings suggest the involvement of cell-cell EphA4 and ephrin-B2 signaling in establishing order in the developing IC.

Response property of inferior collicular neurons inherited from peripheral origin in mouse

The mechanisms underlying spike time coding in auditory system are not well understood. Despite of several models proposed to describe the first spike latency (FSL), there is no comparison of their respective performance. Here, based on FSL data from the central nucleus of inferior colliculus (CIC) in mouse to tone stimuli with varying rise function, rise time, and amplitude, we examined the previous models by comparing the recorded FSL with derived the FSL, respectively. We found that the LIEFTS (leaky integration, event formation, temporal summation) threshold model produced better match with the recorded data than other models. In addition, the model suggested that the short time constants derived from the FSL data (<2ms) cannot be attributed to IC neurons themselves (normally longer than 10ms), but are similar to those for the inner hair cells (around 1.4ms). Our results suggested that LIEFTS threshold model is a better fit for FSL, and FSL properties in central neurons can be inherited along the central auditory pathway, likely through faithful relays from the peripheral origins.

Temporal correlation between auditory neurons and the hippocampal theta rhythm induced by novel stimulations in awake guinea pigs

The hippocampal theta rhythm is associated with the processing of sensory systems such as touch, smell, vision and hearing, as well as with motor activity, the modulation of autonomic processes such as cardiac rhythm, and learning and memory processes. The discovery of temporal correlation (phase locking) between the theta rhythm and both visual and auditory neuronal activity has led us to postulate the participation of such rhythm in the temporal processing of sensory information. In addition, changes in attention can modify both the theta rhythm and the auditory and visual sensory activity. The present report tested the hypothesis that the temporal correlation between auditory neuronal discharges in the inferior colliculus central nucleus (ICc) and the hippocampal theta rhythm could be enhanced by changes in sensory stimulation. We presented chronically implanted guinea pigs with auditory stimuli that varied over time, and recorded the auditory response during wakefulness. It was observed that the stimulation shifts were capable of producing the temporal phase correlations between the theta rhythm and the ICc unit firing, and they differed depending on the stimulus change performed. Such correlations disappeared approximately 6 s after the change presentation. Furthermore, the power of the hippocampal theta rhythm increased in half of the cases presented with a stimulation change. Based on these data, we propose that the degree of correlation between the unitary activity and the hippocampal theta rhythm varies with – and therefore may signal – stimulus novelty.