Inferior Colliculus Of Guinea Pigs Research Articles

Juxtacellular Labeling of Stellate, Disk and Basket Neurons in the Central Nucleus of the Guinea Pig Inferior Colliculus.

We reconstructed the intrinsic axons of 32 neurons in the guinea pig inferior colliculus (IC) following juxtacellular labeling. Biocytin was injected into cells in vivo, after first analyzing physiological response properties. Based on axonal morphology there were two classes of neuron: (1) laminar cells (14/32, 44%) with an intrinsic axon and flattened dendrites confined to a single fibrodendritic lamina and (2) translaminar cells (18/32, 56%) with axons that terminated in two or more laminae in the central nucleus (ICc) or the surrounding cortex. There was also one small, low-frequency cell with bushy-like dendrites that was very sensitive to interaural timing differences. The translaminar cells were subdivided into three groups of cells with: (a) stellate dendrites that crossed at least two laminae (8/32, 25%); (b) flattened dendrites confined to one lamina and that had mainly en passant axonal swellings (7/32, 22%) and (c) short, flattened dendrites and axons with distinctive clusters of large terminal boutons in the ICc (3/32, 9%). These terminal clusters were similar to those of cortical basket cells. The 14 laminar cells all had sustained responses apart from one offset response. Almost half the non-basket type translaminar cells (7/15) had onset responses while the others had sustained responses. The basket cells were the only ones to have short-latency (7–9 ms), chopper responses and this distinctive temporal response should allow them to be studied in more detail in future. This is the first description of basket cells in the auditory brainstem, but more work is required to confirm their neurotransmitter and precise post-synaptic targets.

Frequency-specific activation of the peripheral auditory system using optoacoustic laser stimulation

Hearing impairment is one of the most common sensory deficits in humans. Hearing aids are helpful to patients but can have poor sound quality or transmission due to insufficient output or acoustic feedback, such as for high frequencies. Implantable devices partially overcome these issues but require surgery with limited locations for device attachment. Here, we investigate a new optoacoustic approach to vibrate the hearing organ with laser stimulation to improve frequency bandwidth, not requiring attachment to specific vibratory structures, and potentially reduce acoustic feedback. We developed a laser pulse modulation strategy and simulated its response at the umbo (1–10 kHz) based on a convolution-based model. We achieved frequency-specific activation in which non-contact laser stimulation of the umbo, as well as within the middle ear at the round window and otic capsule, induced precise shifts in the maximal vibratory response of the umbo and neural activation within the inferior colliculus of guinea pigs, corresponding to the targeted, modelled and then stimulated frequency. There was also no acoustic feedback detected from laser stimulation with our experimental setup. These findings open up the potential for using a convolution-based optoacoustic approach as a new type of laser hearing aid or middle ear implant.

Observation of Lidocaine‐suppressed Decrease of Magnesium in Salicylate‐induced Tinnitus with an Online Electrochemical System

AbstractTinnitus, characterized by an auditory perception in the absence of actual sound, is one of the most common encountered difficulties to manage otological problems, in which, lidocaine has been shown to provide temporary relief from subjective tinnitus. However, the pathophysiological mechanism of lidocaine treatment remains to be understood. The study demonstrates the first observation on that lidocaine well suppresses the decrease in the level magnesium (Mg2+) in inferior colliculus (IC) of guinea pigs following salicylate‐induced tinnitus with an online electrochemical system (OECS) for continuously monitoring of microdialysate of Mg2+. The OECS was established by efficiently coupling a selective electrochemical detector with in vivo microdialysis to monitor Mg2+ in the microdialysate continuously sampled from animal brain. The selective detection of Mg2+ over other coexisting neurochemicals was successfully achieved through a mechanism with divalent metal cations (e. g., Mg2+, Ca2+) enhanced catalytic current of organic dyes (i. e., polymerized film of toluidine blue O, p‐TBO) toward the oxidation of nicotinamide adenine dinucleotide (NADH) and with ethyleneglcol‐bis (2‐aminoethylether) tetraacetic acid (EGTA) as selective masking agents for Ca2+. Tinnitus was induced by intraperitoneal injection of sodium salicylate (350 mg/kg body weight). For the lidocaine group, using the microdialysis probe, 1 % lidocaine was perfused into IC of guinea pigs at 2 μL/min for 20 min. With the OECS, we found that the perfusion of lidocaine could recover the decrease of the Mg2+ level caused by salicylate‐induced tinnitus. The basal level of microdialysate Mg2+ in IC of guinea pigs was previously determined to be 1.29±0.44 mM, which was decreased significantly following salicylate‐induced tinnitus. The lidocaine perfusion significantly recovers the Mg2+ level by 37.7±14.8 %. This observation suggests that Mg2+ plays an important role in the pathological mechanism of tinnitus.

Distorting temporal fine structure by phase shifting and its effects on speech intelligibility and neural phase locking

Envelope (E) and temporal fine structure (TFS) are important features of acoustic signals and their corresponding perceptual function has been investigated with various listening tasks. To further understand the underlying neural processing of TFS, experiments in humans and animals were conducted to demonstrate the effects of modifying the TFS in natural speech sentences on both speech recognition and neural coding. The TFS of natural speech sentences was modified by distorting the phase and maintaining the magnitude. Speech intelligibility was then tested for normal-hearing listeners using the intact and reconstructed sentences presented in quiet and against background noise. Sentences with modified TFS were then used to evoke neural activity in auditory neurons of the inferior colliculus in guinea pigs. Our study demonstrated that speech intelligibility in humans relied on the periodic cues of speech TFS in both quiet and noisy listening conditions. Furthermore, recordings of neural activity from the guinea pig inferior colliculus have shown that individual auditory neurons exhibit phase locking patterns to the periodic cues of speech TFS that disappear when reconstructed sounds do not show periodic patterns anymore. Thus, the periodic cues of TFS are essential for speech intelligibility and are encoded in auditory neurons by phase locking.

Individual Differences in Human Auditory Processing: Insights From Single-Trial Auditory Midbrain Activity in an Animal Model.

Auditory-evoked potentials are classically defined as the summations of synchronous firing along the auditory neuraxis. Converging evidence supports a model whereby timing jitter in neural coding compromises listening and causes variable scalp-recorded potentials. Yet the intrinsic noise of human scalp recordings precludes a full understanding of the biological origins of individual differences in listening skills. To delineate the mechanisms contributing to these phenomena, in vivo extracellular activity was recorded from inferior colliculus in guinea pigs to speech in quiet and noise. Here we show that trial-by-trial timing jitter is a mechanism contributing to auditory response variability. Identical variability patterns were observed in scalp recordings in human children, implicating jittered timing as a factor underlying reduced coding of dynamic speech features and speech in noise. Moreover, intertrial variability in human listeners is tied to language development. Together, these findings suggest that variable timing in inferior colliculus blurs the neural coding of speech in noise, and propose a consequence of this timing jitter for human behavior. These results hint both at the mechanisms underlying speech processing in general, and at what may go awry in individuals with listening difficulties.

Influence of the paraflocculus on normal and abnormal spontaneous firing rates in the inferior colliculus

Spontaneous firing rates of neurons in the central auditory pathway, such as in the inferior colliculus, are known to be increased after cochlear trauma. This so-called hyperactivity is thought to be involved in the generation of tinnitus, a phantom auditory perception. Recent research in an animal model suggests behavioural signs of tinnitus can be significantly reduced by silencing or removal of the paraflocculus (PF) of the cerebellum. The current study investigated the effects of acute PF removal on spontaneous firing rates recorded from single neurons in the right inferior colliculus of guinea pigs with normal hearing (which did not receive acoustic trauma) or with hearing loss caused by acoustic trauma. Spontaneous firing rates were obtained at either 2 or 13 weeks after initial surgery on the left side. In half of the animals in each group the left PF was removed immediately prior to the spontaneous firing rates recordings. In the acoustic trauma groups, spontaneous firing rates in the inferior colliculus were higher when the PF was removed compared to animals with an intact PF. This effect of PF removal was not observed in animals that did not receive acoustic trauma. These results suggest that the PF has a tonic inhibitory effect on hyperactivity in the inferior colliculus in animals with hearing loss, but not on normal spontaneous firing rates in normal hearing animals.

A function for binaural integration in auditory grouping and segregation in the inferior colliculus.

Responses of neurons to binaural, harmonic complex stimuli in urethane-anesthetized guinea pig inferior colliculus (IC) are reported. To assess the binaural integration of harmonicity cues for sound segregation and grouping, responses were measured to harmonic complexes with different fundamental frequencies presented to each ear. Simultaneously gated harmonic stimuli with fundamental frequencies of 125 Hz and 145 Hz were presented to the left and right ears, respectively, and recordings made from 96 neurons with characteristic frequencies >2 kHz in the central nucleus of the IC. Of these units, 70 responded continuously throughout the stimulus and were excited by the stimulus at the contralateral ear. The stimulus at the ipsilateral ear excited (EE: 14%; 10/70), inhibited (EI: 33%; 23/70), or had no significant effect (EO: 53%; 37/70), defined by the effect on firing rate. The neurons phase locked to the temporal envelope at each ear to varying degrees depending on signal level. Many of the cells (predominantly EO) were dominated by the response to the contralateral stimulus. Another group (predominantly EI) synchronized to the contralateral stimulus and were suppressed by the ipsilateral stimulus in a phasic manner. A third group synchronized to the stimuli at both ears (predominantly EE). Finally, a group only responded when the waveform peaks from each ear coincided. We conclude that these groups of neurons represent different "streams" of information but exhibit modifications of the response rather than encoding a feature of the stimulus, like pitch.

Predicting neural responses to natural sound in the auditory brainstem

The inferior colliculus is the main processing station in the auditory midbrain and integrates projections from nearly all ascending brainstem nuclei. Apart from being a converging station, the central nucleus of the inferior colliculus (ICC) is essential for extracting time-varying spectrotemporal information [1] and therefore might be important for processing complex sounds such as speech and vocalizations. The ICC has been the target for a human auditory prosthesis [2], which might benefit from model predictions of the neural response in the ICC to incoming sound. Natural sounds such as speech and vocalizations, which display a wide spectrum of acoustic properties, such as harmonics, correlations, amplitude and frequency modulations and are very well suited to study the auditory system. This study is based on several sets of multi-unit activity recorded simultaneously from 32 sites in the contralateral ICC of guinea pigs while acoustically presenting a diverse set of conspecific vocalizations to the right ear. Recordings were taken either along the tonotopic gradient using double-shank electrodes or within iso-frequency lamina using double-tetrode electrodes. We investigated predictive power of several models of temporal responses in the ICC to vocalizations and artificial sound. The tested models include 1) a modified version of the physiologically detailed Meddis Model [4], which was altered in order to match spiking threshold in the guinea pig ICC and to include adaptation effects and output the trial-averaged spiking responses, the peri-stimulus time histograms (PSTH). 2) a generalized linear model and 3) a filtering model with a bandpass filter of 1/3 octaves around the best frequency, with subsequent normalization and rectification for each unit, followed by spatial filtering for nearby units. Predictive power was evaluated by means of the correlation value of the envelope of the PSTHs from the predicted and the experimentally obtained responses. We find that our relatively simple, filtering approach yields surprisingly good overlap of predicted and measured responses for some multi-units, but has poor predictive power for other units. The models (1-2) yield overall better overlap for the whole set of vocalizations but do not perform optimally in predicting the temporal course of the response. Our findings indicate distributions of optimal predictive power in the inferior colliculus over a large best frequency range across and within isofrequency laminae.

Distribution of GABAergic cells in the inferior colliculus that project to the thalamus

A GABAergic component has been identified in the projection from the inferior colliculus (IC) to the medial geniculate body (MG) in cats and rats. We sought to determine if this GABAergic pathway exists in guinea pig, a species widely used in auditory research. The guinea pig IC contains GABAergic cells, but their relative abundance in the IC and their relative contributions to tectothalamic projections are unknown. We identified GABAergic cells with immunochemistry for glutamic acid decarboxylase (GAD) and determined that ~21% of IC neurons are GABAergic. We then combined retrograde tracing with GAD immunohistochemistry to identify the GABAergic tectothalamic projection. Large injections of Fast Blue, red fluorescent beads or FluoroGold were deposited to include all subdivisions of the MG. The results demonstrate a GABAergic pathway from each IC subdivision to the ipsilateral MG. GABAergic cells constitute ~22% of this ipsilateral pathway. In addition, each subdivision of the IC had a GABAergic projection to the contralateral MG. Measured by number of tectothalamic cells, the contralateral projection is about 10% of the size of the ipsilateral projection. GABAergic cells constitute about 20% of the contralateral projection. In summary, the results demonstrate a tectothalamic projection in guinea pigs that originates in part from GABAergic cells that project ipsilaterally or contralaterally to the MG. The results show similarities to both rats and cats, and carry implications for the role of GABAergic tectothalamic projections vis-à-vis the presence (in cats) or near absence (in rats and guinea pigs) of GABAergic interneurons in the MG.

Perineuronal nets and GABAergic cells in the inferior colliculus of guinea pigs

Perineuronal nets (PNs) are aggregates of extracellular matrix that have been associated with neuronal plasticity, critical periods, fast-spiking cells and protection from oxidative stress. Although PNs have been reported in the auditory system in several species, there is disagreement about the distribution of PNs within the inferior colliculus (IC), an important auditory hub in the midbrain. Furthermore, PNs in many brain areas are preferentially associated with GABAergic cells, but whether such an association exists in the IC has not been addressed. We used Wisteria floribunda agglutinin staining and immunohistochemistry in guinea pigs to examine PNs within the IC. PNs are present in all IC subdivisions and are densest in the central portions of the IC. Throughout the IC, PNs are preferentially associated with GABAergic cells. Not all GABAergic cells are surrounded by PNs, so the presence of PNs can be used to subdivide IC GABAergic cells into “netted” and “non-netted” categories. Finally, PNs in the IC, like those in other brain areas, display molecular heterogeneity that suggests a multitude of functions.

The Effect of Correlated Neuronal Firing and Neuronal Heterogeneity on Population Coding Accuracy in Guinea Pig Inferior Colliculus

It has been suggested that the considerable noise in single-cell responses to a stimulus can be overcome by pooling information from a large population. Theoretical studies indicated that correlations in trial-to-trial fluctuations in the responses of different neurons may limit the improvement due to pooling. Subsequent theoretical studies have suggested that inherent neuronal diversity, i.e., the heterogeneity of tuning curves and other response properties of neurons preferentially tuned to the same stimulus, can provide a means to overcome this limit. Here we study the effect of spike-count correlations and the inherent neuronal heterogeneity on the ability to extract information from large neural populations. We use electrophysiological data from the guinea pig Inferior-Colliculus to capture inherent neuronal heterogeneity and single cell statistics, and introduce response correlations artificially. To this end, we generate pseudo-population responses, based on single-cell recording of neurons responding to auditory stimuli with varying binaural correlations. Typically, when pseudo-populations are generated from single cell data, the responses within the population are statistically independent. As a result, the information content of the population will increase indefinitely with its size. In contrast, here we apply a simple algorithm that enables us to generate pseudo-population responses with variable spike-count correlations. This enables us to study the effect of neuronal correlations on the accuracy of conventional rate codes. We show that in a homogenous population, in the presence of even low-level correlations, information content is bounded. In contrast, utilizing a simple linear readout, that takes into account the natural heterogeneity, even of neurons preferentially tuned to the same stimulus, within the neural population, one can overcome the correlated noise and obtain a readout whose accuracy grows linearly with the size of the population.

Auditory cortical axons contact commissural cells throughout the guinea pig inferior colliculus

Projections from auditory cortex (AC) affect how cells in both inferior colliculi (IC) respond to acoustic stimuli. The large projection from the AC to the ipsilateral IC is usually credited with the effects in the ipsilateral IC. The circuitry underlying effects in the contralateral IC is less clear. The direct projection from the AC to the contralateral IC is relatively small. An unexplored possibility is that the large ipsilateral cortical projection contacts the substantial number of cells in the ipsilateral IC that project through the commissure to the contralateral IC.Apparent contacts between cortical boutons and commissural cells were identified in the left IC after injection of different fluorescent tracers into the left AC and the right IC. Commissural cells were labeled throughout the left IC, and many (23–34%) appeared to be contacted by cortical axons. In the central nucleus, both disc-shaped and stellate cells were contacted. Antibodies to glutamic acid decarboxylase (GAD) were used to identify GABAergic commissural cells. The majority (>86%) of labeled commissural cells were GAD-immunonegative. Despite low numbers of GAD-immunopositive commissural cells, some of these cells were contacted by cortical boutons. Nonetheless, most cortically contacted commissural cells were GAD-immunonegative (i.e., presumably glutamatergic).We conclude that auditory cortical axons contact primarily excitatory commissural cells in the ipsilateral IC that project to the contralateral IC. These corticocollicular contacts occur in each subdivision of the ipsilateral IC, suggesting involvement of commissural cells throughout the IC. This pathway – from AC to commissural cells in the ipsilateral IC - is a prime candidate for the excitatory effects of activation of the auditory cortex on responses in the contralateral IC. Overall this suggests that the auditory corticofugal pathway is integrated with midbrain commissural connections.

Auditory Training: Evidence for Neural Plasticity in Older Adults.

Improvements in digital amplification, cochlear implants, and other innovations have extended the potential for improving hearing function; yet, there remains a need for further hearing improvement in challenging listening situations, such as when trying to understand speech in noise or when listening to music. Here, we review evidence from animal and human models of plasticity in the brain's ability to process speech and other meaningful stimuli. We considered studies targeting populations of younger through older adults, emphasizing studies that have employed randomized controlled designs and have made connections between neural and behavioral changes. Overall results indicate that the brain remains malleable through older adulthood, provided that treatment algorithms have been modified to allow for changes in learning with age. Improvements in speech-in-noise perception and cognition function accompany neural changes in auditory processing. The training-related improvements noted across studies support the need to consider auditory training strategies in the management of individuals who express concerns about hearing in difficult listening situations. Given evidence from studies engaging the brain's reward centers, future research should consider how these centers can be naturally activated during training.

Analysis of excitatory synapses in the guinea pig inferior colliculus: A study using electron microscopy and GABA immunocytochemistry

The inferior colliculus (IC) integrates ascending auditory input from the lower brainstem and descending input from the auditory cortex. Understanding how IC cells integrate these inputs requires identification of their synaptic arrangements. We describe excitatory synapses in the dorsal cortex, central nucleus, and lateral cortex of the IC (ICd, ICc and IClc) in guinea pigs. We used electron microscopy (EM) and post-embedding anti-GABA immunogold histochemistry on aldehyde-fixed tissue from pigmented adult guinea pigs. Excitatory synapses were identified by round vesicles, asymmetric synaptic junctions, and gamma-aminobutyric acid-immunonegative (GABA-negative) presynaptic boutons.Excitatory synapses constitute ∼60% of the synapses in each IC subdivision. Three types can be distinguished by presynaptic profile area and number of mitochondrial profiles. Large excitatory (LE) boutons are more than 2μm2 in area and usually contain five or more mitochondrial profiles. Small excitatory (SE) boutons are usually less than 0.7μm2 in area and usually contain 0 or 1 mitochondria. Medium excitatory (ME) boutons are intermediate in size and usually contain 2 to 4 mitochondria. LE boutons are mostly confined to the ICc, while the other two types are present throughout the IC. Dendritic spines are the most common target of excitatory boutons in the IC dorsal cortex, whereas dendritic shafts are the most common target in other IC subdivisions. Finally, each bouton type terminates on both gamma-aminobutyric acid-immunopositive (GABA+) and GABA-negative (i.e., glutamatergic) targets, with terminations on GABA-negative profiles being much more frequent.The ultrastructural differences between the three types of boutons presumably reflect different origins and may indicate differences in postsynaptic effect. Despite such differences in origins, each of the bouton types contact both GABAergic and non-GABAergic IC cells, and could be expected to activate both excitatory and inhibitory IC circuits.

Effects of Cochlear Trauma on BDNF Expression in Guinea Pig Cochlear Nucleus and Inferior Colliculus

Hearing loss caused by cochlear damage results in a variety of plastic changes in the central auditory pathways. One of these is hyperactivity, i.e. increased spontaneous firing rates, which may be involved in the generation of tinnitus, a phantom auditory sensation. The mechanism behind this synaptic plasticity is still uncertain but there may be a role for Brain Derived Neurotrophic Factor (BDNF). The expression of BDNF is activity dependent and BDNF can modulate synaptic plasticity leading to changes in excitability. In the present study we investigated the effects of two different types of cochlear trauma, mechanical and acoustic, at two different time points after trauma, on 1) peripheral hearing loss, 2) hyperactivity in inferior Colliculus (IC) and 3) BDNF protein expression in Cochlear Nucleus (CN) and IC of guinea pigs. BDNF protein expression was determined using ELISA. Although there was no significant difference in the amount of hearing loss between acoustic trauma and mechanical trauma animals, single neuron recordings showed higher levels of hyperactivity after mechanical trauma than after acoustic trauma at two weeks post-recovery from cochlear trauma.In addition, results showed an increase of BDNF levels in the ipsilateral CN and contralateral IC at 2 weeks after mechanical but not after acoustic trauma. BDNF levels recovered to sham control levels in both structures at 6 weeks after cochlear trauma even though hyperactivity remained higher compared to sham surgery animals at the same timepoint. The results suggest a possible time dependent role for BDNF in modulating synaptic plasticity and excitability after mechanical trauma to the cochlea.

Development of hyperactivity after acoustic trauma in the guinea pig inferior colliculus

The time of onset of hyperactivity (increased spontaneous firing rates) was investigated by single neuron recording in the inferior colliculus (IC) of guinea pigs subjected to unilateral acoustic trauma (exposure to a loud 10 kHz tone). Hyperactivity was present by 12 h post acoustic trauma whereas data obtained within approximately 4 h of the cessation of acoustic trauma found no evidence of hyperactivity. These data suggest that hyperactivity in the IC begins at some time between 4 and 12 h post trauma and is a relatively rapid plastic event beginning within hours rather than days post cochlear trauma. This is consistent with results reported in the cat auditory cortex (Norena and Eggermont, 2003). Hyperactivity did not show any further systematic increase between 12 h and up to 2 weeks post acoustic trauma. At recovery times of 12 and 24 h hyperactivity was widespread across most regions of the IC but at longer recovery times, it became progressively more restricted to ventral regions corresponding to the regions of the cochlea where there was persistent damage.

Classification of vocalizations by recordings from the auditory midbrain

The temporal and spatial properties of responses to complex stimuli in the central nucleus of the inferior colliculus (ICC), the main converging station in the auditory midbrain, can provide evidence for coding principles in the auditory system and are relevant for the design of neuroprosthesis. We study responses from guinea pigs to a set of eleven species-specific vocalizations which show a wide range of spectral contents, envelope types, frequency and amplitude modulations. The envelopes of the acoustically presented stimuli are characterized as complex or periodic impulses and have various degrees of periodicity. The frequency content ranges from harmonic strucutres to broad spectral distributions. The data analyzed were multi-unit recordings taken simultaneously from 32 positions in the ICC of guinea pigs using a double shank electrode. Peristimulus time histograms (PSTHs) of the high dimensional recordings were classified by linear discriminant analysis in order to evaluate the spatial and temporal distribution of stimulus-related information without the assumption of a specific coding scheme. Neighboring neural populations respond in a similar manner and have highly correlated PSTHs. Combining responses from different positions improves the classification performance for distant postions which do not show correlation, but not for adjacent positions. Separability of responses along the tonotopic gradient of the ICC to vocalizations shows great variation according to their spectral properties. Low-frequency stimuli are found to be better separable in low characteristic frequency (CF) lamina than complex envelope or broad spectral stimuli. Some stimuli of the latter type (squeal, whistle) are nearly perfectly discriminated in multi-units with high CF whereas discrimination for low-frequency stimuli is less good (60 - 70 %) in this region, see Figure ​Figure1.1. For multi-units positioned in the mid-frequency range along the tonotopic axis all stimuli can be separated at a level similar to the result obtained in the low/high CF regions for the respective preferred stimuli. Figure 1 Confusion matrix for the classification of neural responses to periodic low-frequency stimuli (low chutter, drr) and complex-envelope broad-spectrum stimuli (squeal, low whistle) for a multi-unit in an iso-frequency lamina with a characteristic frequency ... We interpret the results as a consequence of the combination of several frequencies in the vocalizations that are better covered by the widely tuned receptive fields of the neurons in the mid-frequency range than by the receptive fields of the units with CFs in the extreme frequency ranges.

Spontaneous hyperactivity in the auditory midbrain: Relationship to afferent input

Hyperactivity in the form of increased spontaneous firing rates of single neurons develops in the guinea pig inferior colliculus (IC) after unilateral loud sound exposures that result in behavioural signs of tinnitus. The hyperactivity is found in those parts of the topographic frequency map in the IC where neurons possess characteristic frequencies (CFs) closely related to the region in the cochlea where lasting sensitivity changes occur as a result of the loud sound exposure. The observed hyperactivity could be endogenous to the IC, or it could be driven by hyperactivity at lower stages of the auditory pathway. In addition to the dorsal cochlear nucleus (DCN) hyperactivity reported by others, specific cell types in the ventral cochlear nucleus (VCN) also show hyperactivity in this animal model suggesting that increased drive from several regions of the lower brainstem could contribute to the observed hyperactivity in the midbrain. In addition, spontaneous afferent drive from the cochlea itself is necessary for the maintenance of hyperactivity up to about 8 weeks post cochlear trauma. After 8 weeks however, IC hyperactivity becomes less dependent on cochlear input, suggesting that central neurons transition from a state of hyperexcitability to a state in which they generate their own endogenous firing. The results suggest that there might be a “therapeutic window” for early-onset tinnitus, using treatments that reduce cochlear afferent firing.

Binaural Electric-Acoustic Interactions Recorded from the Inferior Colliculus of Guinea Pigs: The Effect of Masking Observed in the Central Nucleus of the Inferior Colliculus

ObjectivesTo investigate the electric-acoustic interactions within the inferior colliculus of guinea pigs and to observe how central masking appears in invasive neural recordings of the inferior colliculus (IC).MethodsA platinum-iridium wire was inserted to scala tympani through cochleostomy with a depth no greater than 1 mm for intracochlear stimulation of electric pulse train. A 5 mm 100 µm, single-shank, thin-film, penetrating recording probe was inserted perpendicularly to the surface of the IC in the coronal plane at an angle of 30-40° off the parasagittal plane with a depth of 2.0-2.5 mm. The peripheral and central masking effects were compared using electric pulse trains to the left ear and acoustic noise to the left ear (ipsilateral) and to the right ear (contralateral). Binaural acoustic stimuli were presented with different time delays and compared with combined electric and acoustic stimuli. The averaged evoked potentials and total spike numbers were measured using thin-film electrodes inserted into the central nucleus of the IC.ResultsIpsilateral noise had more obvious effects on the electric response than did contralateral noise. Contralateral noise decreased slightly the response amplitude to the electric pulse train stimuli. Immediately after the onset of acoustic noise, the response pattern changed transiently with shorter response intervals. The effects of contralateral noise were evident at the beginning of the continuous noise. The total spike number decreased when the binaural stimuli reached the IC most simultaneously.ConclusionThese results suggest that central masking is quite different from peripheral masking and occurs within the binaural auditory system, and this study showed that the effect of masking could be observed in the IC recording. These effects are more evident and consistent with the psychophysical data from spike number analyses than with the previously reported gross potential data.

Deactivation of the inferior colliculus by cooling demonstrates intercollicular modulation of neuronal activity.

The auditory pathways coursing through the brainstem are organized bilaterally in mirror image about the midline and at several levels the two sides are interconnected. One of the most prominent points of interconnection is the commissure of the inferior colliculus (CoIC). Anatomical studies have revealed that these fibers make reciprocal connections which follow the tonotopic organization of the inferior colliculus (IC), and that the commissure contains both excitatory and, albeit fewer, inhibitory fibers. The role of these connections in sound processing is largely unknown. Here we describe a method to address this question in the anaesthetized guinea pig. We used a cryoloop placed on one IC to produce reversible deactivation while recording electrophysiological responses to sounds in both ICs. We recorded single units, multi-unit clusters and local field potentials (LFPs) before, during and after cooling. The degree and spread of cooling was measured with a thermocouple placed in the IC and other auditory structures. Cooling sufficient to eliminate firing was restricted to the IC contacted by the cryoloop. The temperature of other auditory brainstem structures, including the contralateral IC and the cochlea were minimally affected. Cooling below 20°C reduced or eliminated the firing of action potentials in frequency laminae at depths corresponding to characteristic frequencies up to ~8 kHz. Modulation of neural activity also occurred in the un-cooled IC with changes in single unit firing and LFPs. Components of LFPs signaling lemniscal afferent input to the IC showed little change in amplitude or latency with cooling, whereas the later components, which likely reflect inter- and intra-collicular processing, showed marked changes in form and amplitude. We conclude that the cryoloop is an effective method of selectively deactivating one IC in guinea pig, and demonstrate that auditory processing in the IC is strongly influenced by the other.