Search

Disturbances in the neurotransmitter systems associated with the development of temporal lobe epilepsy (TLE) have been well-studied in forebrain structures including the temporal cortex, amygdala, and hippocampus. It is known that in rodents genetically prone to audiogenic seizures, TLE establishment induced by audiogenic kindling is also associated with the involvement of the forebrain, however, initially epileptiform activity arises in the brainstem, in particular, in the inferior colliculi (IC). It is reasonable to suppose that neurochemical alterations in the IC may contribute significantly to the spreading of epileptiform activity at early steps of TLE development. At the same time, the functional state of the key neurotransmitter systems in the IC of audiogenic rodents exposed to audiogenic kindling remains unknown. In the present work, we performed a comprehensive analysis of proteins involved in glutamate- and GABA-ergic transmission in the IC of Krushinsky–Molodkina (KM) rats genetically prone to audiogenic seizures. A modified audiogenic kindling protocol was used to reproduce the early stage of TLE development. According to this protocol, rats were exposed to daily audiogenic stimulations for seven days. Naive KM rats were used as a control. Although the rodent's predisposition to audiogenic seizures is often associated with the impairment of GABAergic transmission, no significant changes were found in the expression of GABA synthesis enzymes and GABAA receptor α1 subunit in the IC of KM rats either 24 hours or a week after their last seizure. However, 24 hours after the last audiogenic stimulation, an increase in glutamatergic transmission in the IC was observed including upregulation of ERK 1/2 kinases, synaptic proteins synapsin 1 and SV2B, VGLUT1 and VGLUT2. One week after the last seizure, only an increase in VGLUT1 content in the IC was observed, suggesting the persistent changes in the neurons of forebrain structures, in particular, of the temporal cortex. [ABSTRACT FROM AUTHOR]

Emergent response properties of sensory neurons depend on circuit connectivity and somatodendritic processing. Neurons of the barn owl's external nucleus of the inferior colliculus (ICx) display emergence of spatial selectivity. These neurons use interaural time difference (ITD) as a cue for the horizontal direction of sound sources. ITD is detected by upstream brainstem neurons with narrow frequency tuning, resulting in spatially ambiguous responses. This spatial ambiguity is resolved by ICx neurons integrating inputs over frequency, a relevant processing in sound localization across species. Previous models have predicted that ICx neurons function as point neurons that linearly integrate inputs across frequency. However, the complex dendritic trees and spines of ICx neurons raises the question of whether this prediction is accurate. Data from in vivo intracellular recordings of ICx neurons were used to address this question. Results revealed diverse frequency integration properties, where some ICx neurons showed responses consistent with the point neuron hypothesis and others with nonlinear dendritic integration. Modeling showed that varied connectivity patterns and forms of dendritic processing may underlie observed ICx neurons' frequency integration processing. These results corroborate the ability of neurons with complex dendritic trees to implement diverse linear and nonlinear integration of synaptic inputs, of relevance for adaptive coding and learning, and supporting a fundamental mechanism in sound localization.

Epilepsy is tightly associated with dysfunction of inhibitory GABA neurotransmission. In this study, Krushinsky–Molodkina (KM) rats genetically prone to audiogenic seizures (AGS) were used. KM rats are characterized by the development of audiogenic epilepsy during postnatal ontogenesis, with AGS onset at the age of 1.5–2 months and fully developed AGS expression by 3rd month. We analyzed GABAergic system of the inferior colliculi (IC) of KM rats at different stages of postnatal development. Wistar rats were used as a control. In the IC of young KM rats, Na+/K+/Cl– cotransporter 1 (NKCC1) expression was increased, while K+/Cl– cotransporter 2 (KCC2) was unchanged indicating impairment of postsynaptic GABA action at early stages of postnatal development. Moreover, we revealed also an increase in the expression of vesicular GABA transporter (VGAT) in the IC which additionally pointed on the higher activity of GABA release. In adult rats, in opposite, we revealed a decrease in the expression of KCC2 transporter indicating downregulation of GABA inhibition on the target cells. Thus, GABA dysregulation in the IC can mediate the seizure susceptibility in adult KM rats. [ABSTRACT FROM AUTHOR]

Dorsal human midbrain contains two nuclei with clear laminar organization, the superior and inferior colliculi. These nuclei extend in depth between the superficial dorsal surface of midbrain and a deep midbrain nucleus, the periaqueductal gray matter (PAG). The PAG, in turn, surrounds the cerebral aqueduct (CA). This study examined the use of two depth metrics to characterize depth and thickness relationships within dorsal midbrain using the superficial surface of midbrain and CA as references. The first utilized nearest-neighbor Euclidean distance from one reference surface, while the second used a level-set approach that combines signed distances from both reference surfaces. Both depth methods provided similar functional depth profiles generated by saccadic eye movements in a functional MRI task, confirming their efficacy for delineating depth for superficial functional activity. Next, the boundaries of the PAG were estimated using Euclidean distance together with elliptical fitting, indicating that the PAG can be readily characterized by a smooth surface surrounding PAG. Finally, we used the level-set approach to measure tissue depth between the superficial surface and the PAG, thus characterizing the variable thickness of the colliculi. Overall, this study demonstrates depth-mapping schemes for human midbrain that enables accurate segmentation of the PAG and consistent depth and thickness estimates of the superior and inferior colliculi.

Sensory processing abnormalities are frequently associated with autism spectrum disorders, but the underlying mechanisms are unclear. Here we studied auditory processing in a mouse model of Fragile X Syndrome (FXS), a leading known genetic cause of autism and intellectual disability. Both humans with FXS and the Fragile X mental retardation gene (Fmr1) knockout (KO) mouse model show auditory hypersensitivity, with the latter showing a strong propensity for audiogenic seizures (AGS) early in development. Because midbrain abnormalities cause AGS, we investigated whether the inferior colliculus (IC) of the Fmr1 KO mice shows abnormal auditory processing compared with wild-type (WT) controls at specific developmental time points. Using antibodies against neural activity marker c-Fos, we found increased density of c-Fos+ neurons in the IC, but not auditory cortex, of Fmr1 KO mice at P21 and P34 following sound presentation. In vivo single-unit recordings showed that IC neurons of Fmr1 KO mice are hyperresponsive to tone bursts and amplitude-modulated tones during development and show broader frequency tuning curves. There were no differences in rate-level responses or phase locking to amplitude-modulated tones in IC neurons between genotypes. Taken together, these data provide evidence for the development of auditory hyperresponsiveness in the IC of Fmr1 KO mice. Although most human and mouse work in autism and sensory processing has centered on the forebrain, our new findings, along with recent work on the lower brainstem, suggest that abnormal subcortical responses may underlie auditory hypersensitivity in autism spectrum disorders.NEW & NOTEWORTHY Autism spectrum disorders (ASD) are commonly associated with sensory sensitivity issues, but the underlying mechanisms are unclear. This study presents novel evidence for neural correlates of auditory hypersensitivity in the developing inferior colliculus (IC) in Fmr1 knockout (KO) mouse, a mouse model of Fragile X Syndrome (FXS), a leading genetic cause of ASD. Responses begin to show genotype differences between postnatal days 14 and 21, suggesting an early developmental treatment window.

Hydrogen sulfide (H2S) is a gaseous molecule found naturally in the environment, and as an industrial byproduct, and is known to cause acute death and induces long-term neurological disorders following acute high dose exposures. Currently, there is no drug approved for treatment of acute H2S-induced neurotoxicity and/or neurological sequelae. Lack of a deep understanding of pathogenesis of H2S-induced neurotoxicity has delayed the development of appropriate therapeutic drugs that target H2S-induced neuropathology. RNA sequencing analysis was performed to elucidate the cellular and molecular mechanisms of H2S-induced neurodegeneration, and to identify key molecular elements and pathways that contribute to H2S-induced neurotoxicity. C57BL/6J mice were exposed by whole body inhalation to 700 ppm of H2S for either one day, two consecutive days or 4 consecutive days. Magnetic resonance imaging (MRI) scan analyses showed H2S exposure induced lesions in the inferior colliculus (IC) and thalamus (TH). This mechanistic study focused on the IC. RNA Sequencing analysis revealed that mice exposed once, twice, or 4 times had 283, 193 and 296 differentially expressed genes (DEG), respectively (q-value < 0.05, fold-change> 1.5). Hydrogen sulfide exposure modulated multiple biological pathways including unfolded protein response, neurotransmitters, oxidative stress, hypoxia, calcium signaling, and inflammatory response in the IC. Hydrogen sulfide exposure activated PI3K/Akt and MAPK signaling pathways. Pro-inflammatory cytokines were shown to be potential initiators of the modulated signaling pathways following H2S exposure. Furthermore, microglia were shown to release IL-18 and astrocytes released both IL-1β and IL-18 in response to H2S. This transcriptomic analysis data revealed complex signaling pathways involved in H2S-induced neurotoxicity and may provide important associated mechanistic insights.

Methylmercury (MeHg) is well known to induce auditory disorders such as dysarthria. When we performed a global analysis on the brains of mice exposed to MeHg by magnetic resonance imaging, an increase in the T1 signal in the inferior colliculus (IC), which is localized in the auditory pathway, was observed. Therefore, the purpose of this study is to examine the pathophysiology and auditory dysfunction induced by MeHg, focusing on the IC. Measurement of the auditory brainstem response revealed increases in latency and decreases in threshold in the IC of mice exposed to MeHg for 4 weeks compared with vehicle mice. Incoordination in MeHg-exposed mice was noted after 6 weeks of exposure, indicating that IC dysfunction occurs earlier than incoordination. There was no change in the number of neurons or microglial activity, while the expression of glial fibrillary acidic protein, a marker for astrocytic activity, was elevated in the IC of MeHg-exposed mice after 4 weeks of exposure, indicating that astrogliosis occurs in the IC. Suppression of astrogliosis by treatment with fluorocitrate exacerbated the latency and threshold in the IC evaluated by the auditory brainstem response. Therefore, astrocytes in the IC are considered to play a protective role in the auditory pathway. Astrocytes exposed to MeHg increased the expression of brain-derived neurotrophic factor in the IC, suggesting that astrocytic brain-derived neurotrophic factor is a potent protectant in the IC. This study showed that astrogliosis in the IC could be an adaptive response to MeHg toxicity. The overall toxicity of MeHg might be determined on the basis of the balance between MeHg-mediated injury to neurons and protective responses from astrocytes.

Electrical stimulation of the auditory nerve with a penetrating intraneural (IN) electrode in acutely deafened cats produces much more restricted spread of excitation than is obtained in that preparation with a conventional cochlear implant (CI) as reported by Middlebrooks and Snyder (J Assoc Res Otolaryngol 8:258-279, 2007). That suggests that a future auditory prosthesis employing IN stimulation might offer human patients greater frequency selectivity than is available with a present-day CI. Nevertheless, it is a concern that the electrical field produced by an IN electrode might be too restricted to produce adequate stimulation of the partially depopulated auditory nerve of a deaf patient. We evaluated this by testing responses to IN and CI stimulation in adult-deafened cats. Activation of the auditory pathway was monitored by recording from the central nucleus of the inferior colliculus (ICC). Cats deaf for 153-277 days exhibited a ~ 30 % loss of auditory nerve fibers compared to cats deaf for

Acute exposure to high concentrations of H2S causes severe brain injury and long-term neurological disorders, but the mechanisms involved are not known. To better understand the cellular and molecular mechanisms involved in acute H2S-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to identify key molecules and molecular pathways involved in the pathogenesis of acute H2S-induced neurotoxicity and neurodegeneration. Mice were subjected to acute inhalation exposure of up to750 ppm of H2S. H2S induced behavioral deficits and severe lesions including hemorrhage in the inferior colliculus (IC). The IC was microdissected for proteomic analysis. Tandem mass tags (TMT) liquid chromatography mass spectrometry (LC-MS/MS)-based quantitative proteomics was applied for protein identification and quantitation. LC-MS/MS identified 598, 562, and 546 altered proteomic changes at 2 h, and on days 2 and 4 post-H2S exposure, respectively. Of these, 77 proteomic changes were statistically significant at any of the 3 time points. Mass spectrometry data were subjected to Perseus 1.5.5.3 statistical analysis, and gene ontology heat map clustering. Expressions of several key molecules were verified to confirm H2S-dependent proteomics changes. Webgestalt pathway overrepresentation enrichment analysis with Panther engine revealed H2S exposure disrupted several biological processes including metabotropic glutamate receptor group 1 and inflammation mediated by chemokine and cytokine signaling pathways among others. Further analysis showed that energy metabolism, integrity of blood-brain barrier, hypoxic, and oxidative stress signaling pathways were also implicated. Collectively, this broad-spectrum proteomics data has provided important clues to follow up in future studies to further elucidate mechanisms of H2S-induced neurotoxicity.

Introduction. Subcortical auditory centers have several sources of blood supply. Cochlear nuclei are vascularized by the anterior inferior cerebellar artery. Superior cerebellar and posterior cerebral arteries supply the inferior colliculus nucleus, while the medial geniculate body nucleus is supplied by several posterior cerebral artery branches. The aim of the research was to quantify the vascular network of subcortical auditory centers. Methods. Twelve adult brains, both sexes, aged 21 to 78 years, without signs of neurological diseases were analyzed in this study. Samples for histological sections, stained by the Mallory method, were obtained from strata cut at levels: the junction of the middle and rostral thirds of the oliva, the inferior colliculi, and the thalamic pulvinar. Volume, surface, and length density of the vascular network of subcortical auditory centers were analyzed stereological parameters. Results. All parameters had the highest values in the medial geniculate body nucleus. Statistically significant difference was found in the volume, surface, and length density between vascular networks of the cochlear nuclei and medial geniculate body nucleus, and between inferior colliculus nuclei and medial geniculate body. Vessels in cochlear nuclei and inferior colliculus nuclei differed only in length density. Conclusion. Cochlear nuclei and inferior colliculi nuclei blood vessels have a similar density and diameter, but vessels in inferior colliculi nuclei are more tortuous. In the medial geniculate body nucleus vessels are larger, denser and more tortuous compared to the other two subcortical auditory centers

In this review of neuroanatomical studies of the genetically epilepsy-prone rat (GEPR), three main topics will be covered. First, the number of GABAergic neurons and total neurons in the inferior colliculus of GEPRs will be compared to those of the nonepileptic Sprague-Dawley rat. Next, the number of small neurons in the inferior colliculus will be described in both developmental and genetic analyses of GEPRs and their backcrosses. Last, results from two types of studies on the propagation pathways for audiogenic seizures in GEPRs will be shown. Together, these studies demonstrate a unique GABAergic, small neuron defect in the inferior colliculus of GEPRs that may play a vital role in the initiation and spread of seizure activity during audiogenic seizures. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

Stream segregation enables a listener to disentangle multiple competing sequences of sounds. A recent study from our laboratory demonstrated that cortical neurons in anesthetized cats exhibit spatial stream segregation (SSS) by synchronizing preferentially to one of two sequences of noise bursts that alternate between two source locations. Here, we examine the emergence of SSS along the ascending auditory pathway. Extracellular recordings were made in anesthetized rats from the inferior colliculus (IC), the nucleus of the brachium of the IC (BIN), the medial geniculate body (MGB), and the primary auditory cortex (A1). Stimuli consisted of interleaved sequences of broadband noise bursts that alternated between two source locations. At stimulus presentation rates of 5 and 10 bursts per second, at which human listeners report robust SSS, neural SSS is weak in the central nucleus of the IC (ICC), it appears in the nucleus of the brachium of the IC (BIN) and in approximately two-thirds of neurons in the ventral MGB (MGBv), and is prominent throughout A1. The enhancement of SSS at the cortical level reflects both increased spatial sensitivity and increased forward suppression. We demonstrate that forward suppression in A1 does not result from synaptic inhibition at the cortical level. Instead, forward suppression might reflect synaptic depression in the thalamocortical projection. Together, our findings indicate that auditory streams are increasingly segregated along the ascending auditory pathway as distinct mutually synchronized neural populations.Significance statementListeners 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.

The ability to segregate simultaneous sound sources based on their spatial locations is an important aspect of auditory scene analysis. While the role of sound azimuth in segregation is well studied, the contribution of sound elevation remains unknown. Although previous studies in humans suggest that elevation cues alone are not sufficient to segregate simultaneous broadband sources, the current study demonstrates they can suffice. Listeners segregating a temporally modulated noise target from a simultaneous unmodulated noise distracter differing in elevation fall into two statistically distinct groups: one that identifies target direction accurately across a wide range of modulation frequencies (MF) and one that cannot identify target direction accurately and, on average, reports the opposite direction of the target for low MF. A non-spiking model of inferior colliculus neurons that process single-source elevation cues suggests that the performance of both listener groups at the population level can be accounted for by the balance of excitatory and inhibitory inputs in the model. These results establish the potential for broadband elevation cues to contribute to the computations underlying sound source segregation and suggest a potential mechanism underlying this contribution.

Locations of sounds are computed in the central auditory pathway based primarily on differences in sound level and timing at the two ears. In rats, the results of that computation appear in the primary auditory cortex (A1) as exclusively contralateral hemifield spatial sensitivity, with strong responses to sounds contralateral to the recording site, sharp cutoffs across the midline, and weak, sound-level-tolerant responses to ipsilateral sounds. We surveyed the auditory pathway in anesthetized rats to identify the brain level(s) at which level-tolerant spatial sensitivity arises. Noise-burst stimuli were varied in horizontal sound location and in sound level. Neurons in the central nucleus of the inferior colliculus (ICc) displayed contralateral tuning at low sound levels, but tuning was degraded at successively higher sound levels. In contrast, neurons in the nucleus of the brachium of the inferior colliculus (BIN) showed sharp, level-tolerant spatial sensitivity. The ventral division of the medial geniculate body (MGBv) contained two discrete neural populations, one showing broad sensitivity like the ICc and one showing sharp sensitivity like A1. Dorsal, medial, and shell regions of the MGB showed fairly sharp spatial sensitivity, likely reflecting inputs from A1 and/or the BIN. The results demonstrate two parallel brainstem pathways for spatial hearing. The tectal pathway, in which sharp, level-tolerant spatial sensitivity arises between ICc and BIN, projects to the superior colliculus and could support reflexive orientation to sounds. The lemniscal pathway, in which such sensitivity arises between ICc and the MGBv, projects to the forebrain to support perception of sound location.

Experience-dependent formation of synaptic input clusters can occur in juvenile brains. Whether this also occurs in adults is largely unknown. We previously reconstructed the normal and learned circuits of prism-adapted barn owls and found that changes in clustering of axo-dendritic contacts (putative synapses) predicted functional circuit strength. Here we asked whether comparable changes occurred in normal and prism-removed adults. Across all anatomical zones, no systematic differences in the primary metrics for within-branch or between-branch clustering were observed: 95-99% of contacts resided within clusters (

Neurons expressing the calcium binding proteins (CaBPs) parvalbumin (PV) and calbindin (CB) have shown age-related density changes throughout the ascending auditory system of both rodents and macaque monkeys. In the cerebral cortex, neurons expressing these CaBPs express markers of γ-aminobutyric acidergic neurotransmission, such as GAD67, and have well-understood physiological response properties. Recent evidence suggests that, in the rodent auditory brainstem, CaBP-containing cells do not express GAD67. It is unknown whether PV- and CB-containing cells in subcortical auditory structures of macaques similarly do not express GAD67, and a better understanding of the neurotransmission of neurons expressing these proteins is necessary for understanding the age-related changes in their density throughout the macaque auditory system. This was investigated with immunofluorescent double-labeling techniques to coregister PV- and CB-expressing neurons with GAD67 in the superior olivary complex and the inferior colliculus of young and aged rhesus macaques. The proportions of GAD67-expressing PV- and CB-positive neurons were computed with unbiased sampling techniques. Our results indicate that between 42% and 62% of PV- and CB-positive neurons in the auditory brainstem and midbrain express GAD67, which is significantly less than in the cerebrum. In general, fewer PV(+) neurons and more CB(+) neurons expressed GAD67 as a function of age. These results demonstrate that the inhibitory molecular profile of PV- and CB-expressing neurons can change with age in subcortical auditory structures and that these neurons are distinct from the well-described inhibitory interneurons that express these proteins in the cerebral cortex.

This study aimed to explore gene expression changes in the inferior colliculus (IC) after single-sided deafness (SSD). Forty 8-week-old female Sprague–Dawley rats were used. Twenty rats underwent right-side cochlear ablation, and IC tissues were harvested after 2 weeks (SSD 2-week group). Twenty rats underwent a sham operation and were sacrificed after 2 weeks (control group). Both sides of the IC were analyzed using a gene expression array. Pathway analyses were performed on genes that were differentially expressed compared with their levels in the control group. The expression levels of genes involved in the candidate pathways were confirmed using reverse transcription polymerase chain reaction (RT-PCR). Among the genes with ≥ 1.5-fold changes in expression levels and P < 0.05, there were 7 and 9 genes with increased and decreased expression, respectively, in the ipsilateral IC and 10 and 12 genes with increased and decreased expression, respectively, in the contralateral IC. The pathway analysis did not identify significantly related pathway. In the bilateral analysis, a total of 14 genes were ≥ 1.3-fold downregulated in both the ipsilateral and contralateral IC in the SSD 2-week group compared with their expression in the control group. Pathway analyses of these 14 genes included 7 genes, namely, amine compound solute carrier (Slc)5a7; Slc18a3; Slc6a5; synaptic vesicle glycoprotein 2C (Sv2c); S100 calcium binding protein A10 (S100a10); a gene with sequence similarity to family 111, member A (Fam111a); and peripherin (Prph), that were related to the acetylcholine neurotransmitter release cycle, SLC transporters, and the neurotransmitter release cycle pathways. RT-PCR showed reduced expression of Slc5a7, Sv2c, and Prph in the contralateral IC and Slc18a3 and Slc6a5 in the ipsilateral IC of the SSD 2-week group compared with that in the control group. [ABSTRACT FROM AUTHOR]

ObjectiveAn abnormality in auditory evoked responses localised to the inferior colliculus (IC) has been reported in rapid eye movement (REM) sleep behaviour disorder (RBD) patients. The external cortex of the inferior colliculus (ICX) has been demonstrated not only to be involved in auditory processing, but also to participate in the modulation of motor activity.MethodsRats were surgically implanted with electrodes for electroencephalography (EEG) and electromyography (EMG) recording and guide cannulae aimed at the ICX for drug infusions. Drug infusions were conducted after the animals recovered from surgery. Polysomnographic recordings with video were analysed to detect normal and abnormal sleep states.ResultsBaclofen, a gamma-aminobutyric acid B (GABAB) receptor agonist, infused into the ICX increased phasic motor activity in slow-wave sleep (SWS) and REM sleep and tonic muscle activity in REM sleep; it also elicited RBD-like activity during the infusion and post-infusion period. In contrast, saclofen, a GABAB receptor antagonist, did not produce significant changes in motor activities in sleep. Baclofen infusions in ICX also significantly increased REM sleep during the post-infusion period, while saclofen infusions did not change the amount of any sleep-waking states.ConclusionsThis study suggests that GABAB receptor mechanisms in the ICX may be implicated in the pathology of RBD.

Previous cochlear implant studies using isolated electrical stimulus pulses in animal models have reported that intracochlear monopolar stimulus configurations elicit broad extents of neuronal activation within the central auditory system-much broader than the activation patterns produced by bipolar electrode pairs or acoustic tones. However, psychophysical and speech reception studies that use sustained pulse trains do not show clear performance differences for monopolar versus bipolar configurations. To test whether monopolar intracochlear stimulation can produce selective activation of the inferior colliculus, we measured activation widths along the tonotopic axis of the inferior colliculus for acoustic tones and 1,000-pulse/s electrical pulse trains in guinea pigs and cats. Electrical pulse trains were presented using an array of 6-12 stimulating electrodes distributed longitudinally on a space-filling silicone carrier positioned in the scala tympani of the cochlea. We found that for monopolar, bipolar, and acoustic stimuli, activation widths were significantly narrower for sustained responses than for the transient response to the stimulus onset. Furthermore, monopolar and bipolar stimuli elicited similar activation widths when compared at stimulus levels that produced similar peak spike rates. Surprisingly, we found that in guinea pigs, monopolar and bipolar stimuli produced narrower sustained activation than 60 dB sound pressure level acoustic tones when compared at stimulus levels that produced similar peak spike rates. Therefore, we conclude that intracochlear electrical stimulation using monopolar pulse trains can produce activation patterns that are at least as selective as bipolar or acoustic stimulation.

High intensity noise exposure leads to a permanent shift in auditory thresholds (PTS), affecting both peripheral (cochlear) tissue and the central auditory system. Studies have shown that a noise-induced hearing loss results in significant cell loss in several auditory structures. Degeneration can be demonstrated within hours after noise exposure, particularly in the lower auditory pathway, and continues to progress over days and weeks following the trauma. However, there is limited knowledge about the effects of recurring acoustic trauma. Repeated noise exposure has been demonstrated to increase neuroplasticity and neural activity. Thus, the present study aimed to investigate the influence of a second noise exposure on the cytoarchitecture of key structures of the auditory pathway, including spiral ganglion neurons (SGN), the ventral and dorsal cochlear nucleus (VCN and DCN, respectively), and the inferior colliculus (IC). In the experiments, young adult normal hearing mice were exposed to noise once or twice (with the second trauma applied one week after the initial exposure) for 3 h, using broadband white noise (5 - 20 kHz) at 115 dB SPL. The cell densities in the investigated auditory structures significantly decreased in response to the initial noise exposure compared to unexposed control animals. These findings are consistent with earlier research, which demonstrated degeneration in the auditory pathway within the first week after acoustic trauma. Additionally, cell densities were significantly decreased after the second trauma, but this effect was only observed in the VCN, with no similar effects seen in the SGN, DCN, or IC. These results illustrate how repeated noise exposure influences the cytoarchitecture of the auditory system. It appears that an initial noise exposure primarily damages the lower auditory pathway, but surviving cellular structures may develop resistance to additional noise-induced injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Immunocytochemistry was used to study the distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subtypes in the inferior colliculus (IC) of genetically epilepsy-prone rats (GEPR-9s) and normal Sprague-Dawley (SD) rats. The analysis was conducted using 3 antibodies specific for glutamate receptor subtypes, GluR 1, GluR 2/3, and GluR 4. Light microscopy showed that immunostaining of the IC was most dense with the GluR 2/3 antibody for both strains of animals. The amount of GluR 2/3 immunolabeling was similar for sound-stimulated GEPR-9s, seizure-naive GEPR-9s, and SD rats. The electron microscopy of GluR 2/3 in the IC revealed immunoreaction products associated with the postsynaptic densities of asymmetric synapses. The thin sections had comparable amounts of reaction product in dendrites or dendritic spines for both strains. Since the distribution and quantity of AMPA receptors in the IC of GEPR-9s and SD rats are similar, our results indicate that altered AMPA receptors are probably not the primary cause of seizure initiation in GEPR-9s.

Previous studies have shown the functional importance of the inferior colliculus (IC) for the propagation and initiation of audiogenic seizures in several models of epilepsy in rats. A review of the cell types and cytoarchitecture of the IC, including its three major subdivisions, is presented. Significant increases in GABA levels and the number of GABAergic neurons are found in the central nucleus of the IC (ICCN) of genetically epilepsy-prone rats (GEPR-9s) as compared to Sprague-Dawley rats that do not display audiogenic seizures. Two independent anatomical methods were used to determine the number of GABAergic neurons, immunocytochemistry and in situ hybridization. In both types of preparation, the labeled cells in the ICCN appeared to be of different sizes but the number of small cells with diameters less than 15 microns showed the greatest increase. Nissl-stained sections showed that the total number of neurons in the ICCN was increased in GEPR-9s and indicated that the increase in GABAergic neurons was not due to a change in the phenotype of collicular neurons from non-GABAergic to GABAergic. The number of small neurons in Nissl-stained sections of the ICCN was shown to correlate with seizure severity in the offspring of crosses made between Sprague-Dawley rats and GEPR-9s. Furthermore, the GEPR-3s that display moderate seizures showed a significant increase in the number of small neurons in the ICCN, and the magnitude of this increase was predicted from this correlation. Finally, the use of knife cuts through the midbrain indicated that the ICCN sends an important projection to the external nucleus and that this projection plays a vital role in the propagation of seizure activity from the site of seizure initiation in the ICCN. It remains to be resolved how the increase in small GABAergic neurons in the ICCN is responsible for the known pharmacological defects observed at GABAergic synapses.

Previous studies have shown the functional importance of the inferior colliculus (IC) for the propagation and initiation of audiogenic seizures in several models of epilepsy in rats. A review of the cell types and cytoarchitecture of the IC, including its three major subdivisions, is presented. Significant increases in GABA levels and the number of GABAergic neurons are found in the central nucleus of the IC (ICCN) of genetically epilepsy-prone rats (GEPR-9s) as compared to Sprague-Dawley rats that do not display audiogenic seizures. Two independent anatomical methods were used to determine the number of GABAergic neurons, immunocytochemistry and in situ hybridization. In both types of preparation, the labeled cells in the ICCN appeared to be of different sizes but the number of small cells with diameters less than 15 microns showed the greatest increase. Nissl-stained sections showed that the total number of neurons in the ICCN was increased in GEPR-9s and indicated that the increase in GABAergic neurons was not due to a change in the phenotype of collicular neurons from non-GABAergic to GABAergic. The number of small neurons in Nissl-stained sections of the ICCN was shown to correlate with seizure severity in the offspring of crosses made between Sprague-Dawley rats and GEPR-9s. Furthermore, the GEPR-3s that display moderate seizures showed a significant increase in the number of small neurons in the ICCN, and the magnitude of this increase was predicted from this correlation. Finally, the use of knife cuts through the midbrain indicated that the ICCN sends an important projection to the external nucleus and that this projection plays a vital role in the propagation of seizure activity from the site of seizure initiation in the ICCN. It remains to be resolved how the increase in small GABAergic neurons in the ICCN is responsible for the known pharmacological defects observed at GABAergic synapses.

Previous studies have shown significantly greater GABA levels and numbers of GABAergic neurons in the central nucleus of the inferior colliculus (ICCN) of genetically epilepsy-prone rats (GEPR-9s). In the present study, in situ hybridization and emulsion autoradiographic techniques were used to determine whether there are also elevated numbers of ICCN cells that contain the 67-kD form of mRNA for the GABA synthesizing enzyme, glutamate decarboxylase (GAD), in GEPR-9s as compared to normal Sprague-Dawley (SD) rats. Hybridization with a 35S-labeled RNA probe complementary to a span of monkey GAD mRNA labeled cells throughout the brain including the ICCN. Labeled cells in the ICCN appeared to be of different sizes that corresponded with previous descriptions of GABAergic neurons from immunocytochemical studies. In the GEPR-9s, a larger number of GAD67 cRNA labeled neurons was observed in the ICCN as compared to SD rats. The external nucleus of the inferior colliculus was also found to contain significantly greater numbers of GAD67 cRNA labeled neurons whereas in the frontal cortex, a region of the brain that is not required for audiogenic seizure activity in GEPR-9s, there were no significant differences in hybridization between GEPR-9s and SD rats. Interestingly, within the superficial layers of the superior colliculus there was a higher density of hybridization in GEPR-9s than in SD rats indicating higher levels of GAD expression.(ABSTRACT TRUNCATED AT 250 WORDS)