Regions Of Inferior Colliculus Research Articles

Age-related upregulation of dense core vesicles in the central inferior colliculus.

Presbycusis is one of the most prevalent disabilities in aged populations of industrialized countries. As we age less excitation reaches the central auditory system from the periphery. To compensate, the central auditory system [e.g., the inferior colliculus (IC)], downregulates GABAergic inhibition to maintain homeostatic balance. However, the continued downregulation of GABA in the IC causes a disruption in temporal precision related to presbycusis. Many studies of age-related changes to neurotransmission in the IC have therefore focused on GABAergic systems. However, we have discovered that dense core vesicles (DCVs) are significantly upregulated with age in the IC. DCVs can carry neuropeptides, co-transmitters, neurotrophic factors, and proteins destined for the presynaptic zone to participate in synaptogenesis. We used immuno transmission electron microscopy across four age groups (3-month; 19-month; 24-month; and 28-month) of Fisher Brown Norway rats to examine the ultrastructure of DCVs in the IC. Tissue was stained post-embedding for GABA immunoreactivity. DCVs were characterized by diameter and by the neurochemical profile (GABAergic/non-GABAergic) of their location (bouton, axon, soma, and dendrite). Our data was collected across the dorsolateral to ventromedial axis of the central IC. After quantification, we had three primary findings. First, the age-related increase of DCVs occurred most robustly in non-GABAergic dendrites in the middle and low frequency regions of the central IC during middle age. Second, the likelihood of a bouton having more than one DCV increased with age. Lastly, although there was an age-related loss of terminals throughout the IC, the proportion of terminals that contained at least one DCV did not decline. We interpret this finding to mean that terminals carrying proteins packaged in DCVs are spared with age. Several recent studies have demonstrated a role for neuropeptides in the IC in defining cell types and regulating inhibitory and excitatory neurotransmission. Given the age-related increase of DCVs in the IC, it will be critical that future studies determine whether (1) specific neuropeptides are altered with age in the IC and (2) if these neuropeptides contribute to the loss of inhibition and/or increase of excitability that occurs during presbycusis and tinnitus.

Contralateral tinnitus and hearing loss due to a tumor at the region of inferior colliculus: illustrative case.

BACKGROUNDSubjective hearing loss resulting from unilateral lesions of the quadrigeminal cistern region or inferior colliculus is a rare entity.OBSERVATIONSThe authors presented the case of a 32-year-old man with a history of 4 months of nonpulsatile tinnitus and 1 month of unilateral sensorineural hearing loss. He was otherwise healthy with no significant previous medical history. Intravenous gadolinium contrast magnetic resonance imaging of the head revealed a lesion at the region of the left inferior colliculus suggestive of a lipoma. The tumor was removed, and the patient had no significant hearing change afterward, with an improvement in tinnitus. The histological examination demonstrated the tumor as a fibrolipoma.LESSONSContralateral subjective hearing loss is an uncommon presentation for a lesion in the region of the inferior colliculus.

Mismatch of structural and functional tonotopy for natural sounds in the auditory midbrain

Neurons in the auditory system are spatially organized in their responses to pure tones, and this tonotopy is expected to predict neuronal responses to more complex sounds such as vocalizations. We presented vocalizations with low-, medium- and high-frequency content to determine if selectivity of neurons in the inferior colliculus (IC) of mice respects the tonotopic spatial structure. Tonotopy in the IC predicts that neurons located in dorsal regions should only respond to low-frequency vocalizations and only neurons located in ventral regions should respond to high-frequency vocalizations. We found that responses to vocalizations were independent of location, and many neurons in the dorsal, low-frequency region of IC responded to high-frequency vocalizations. To test whether this was due to dorsal neurons having broad frequency tuning curves, we convolved each neuron’s frequency tuning curve with each vocalization, and found that the tuning curves were not good predictors of the actual neural responses to the vocalizations. We then used a nonlinear model of signal transduction in the cochlea that generates distortion products to predict neural responses to the vocalizations. We found that these predictions more closely matched the actual neural responses. Our findings suggest that the cochlea distorts the frequency representation in vocalizations and some neurons use this distorted representation to encode the vocalizations.

The level and distribution of the GABABR1 and GABABR2 receptor subunits in the rat's inferior colliculus

The type B γ-aminobutyric acid receptor (GABAB receptor) is an important neurotransmitter receptor in the midbrain auditory structure, the inferior colliculus (IC). A functional GABAB receptor is a heterodimer consisting of two subunits, GABABR1 and GABABR2. Western blotting and immunohistochemical experiments were conducted to examine the expression of the two subunits over the IC including its central nucleus, dorsal cortex, and external cortex (ICc, ICd, and ICx). Results revealed that the two subunits existed in both cell bodies and the neuropil throughout the IC. The two subunits had similar regional distributions over the IC. The combined level of cell body and neuropil labeling was higher in the ICd than the other two subdivisions. Labeling in the ICc and ICx was stronger in the dorsal than the ventral regions. In spite of regional differences, no defined boundaries were formed between different areas. For both subunits, the regional distribution of immunoreactivity in the neuropil was parallel to that of combined immunoreactivity in the neuropil and cell bodies. The density of labeled cell bodies tended to be higher but sizes of cell bodies tended to be smaller in the ICd than in the other subdivisions. No systematic regional changes were found in the level of cell body immunoreactivity, except that GABABR2-immunoreactive cell bodies in the ICd had slightly higher optic density (OD) than in other regions. Elongated cell bodies existed throughout the IC. Many labeled cell bodies along the outline of the IC were oriented in parallel to the outline. No strong tendency of orientation was found in labeled cell bodies in ICc. Regional distributions of the subunits in ICc correlated well with inputs to this subdivision. Our finding regarding the contrast in the level of neuropil immunoreactivity among different subdivisions is consistent with the fact that the GABAB receptor has different pre- and postsynaptic functions in different IC regions.

Computer-assisted 3-D reconstructions of Golgi-impregnated neurons in the cortical regions of the inferior colliculus of rat

The inferior colliculus (IC) is the main auditory nucleus in the midbrain. This auditory center is made of a central nucleus (CNIC) characterized by a distinct laminar organization that is surrounded by cortical regions. The neuronal types in the CNIC are well established but thus far, the neuronal composition and functional roles of the cortical regions are not fully appreciated. As dendritic architecture is critical for the synaptic integrative properties of neurons, a detailed analysis of the dendritic architecture of the neurons in the collicular cortical regions should shed light on our understanding of their roles in collicular function. In the present study, we have used the del Rio-Hortega Golgi procedure to impregnate individual neurons within the IC. Rat brains were embedded in resin and sectioned serially to allow quantitative 3-D analyses of single neurons or groups of neurons. Our results demonstrate that the cortical regions of the IC are made up of unique sets of neuronal types and that there is an interdigitation of dendrites at the cortical borders. This latter feature may have led to difficulty in delineating a sharp border between the CNIC and cortical regions in previous studies. The quantitative analysis further demonstrates that there are significant differences in many of the dendritic parameters tested when compared to the neurons from the CNIC. Moreover, we observed that the neuronal populations of the cortical regions vary from the laminar pattern of the CNIC and from each other. Since the main organizing principle of the CNIC is the laminar organization of ‘flat’ neurons, evidence that cortical IC regions lack flat neurons supports the subdivision schema presented here.

Statistical mapping of sound-evoked activity in the mouse auditory midbrain using Mn-enhanced MRI

Manganese-enhanced MRI (MEMRI) has been developed to image brain activity in small animals, including normal and genetically modified mice. Here, we report the use of a MEMRI-based statistical parametric mapping method to analyze sound-evoked activity in the mouse auditory midbrain, the inferior colliculus (IC). Acoustic stimuli with defined frequency and amplitude components were shown to activate and enhance neuronal ensembles in the IC. These IC activity patterns were analyzed quantitatively using voxel-based statistical comparisons between groups of mice with or without sound stimulation. Repetitive 40-kHz pure tone stimulation significantly enhanced ventral IC regions, which was confirmed in the statistical maps showing active regions whose volumes increased in direct proportion to the amplitude of the sound stimuli (65 dB, 77 dB, and 89 dB peak sound pressure level). The peak values of the activity-dependent MEMRI signal enhancement also increased from 7% to 20% for the sound amplitudes employed. These results demonstrate that MEMRI statistical mapping can be used to analyze both the 3D spatial patterns and the magnitude of activity evoked by sound stimuli carrying different energy. This represents a significant advance in the development of MEMRI for quantitative and unbiased analysis of brain function in the deep brain nuclei of mice.

Antidromic Activation Reveals Tonotopically Organized Projections From Primary Auditory Cortex to the Central Nucleus of the Inferior Colliculus in Guinea Pig

The inferior colliculus (IC) is highly modulated by descending projections from higher auditory and nonauditory centers. Traditionally, corticofugal fibers were believed to project mainly to the extralemniscal IC regions. However, there is some anatomical evidence suggesting that a substantial number of fibers from the primary auditory cortex (A1) project into the IC central nucleus (ICC) and appear to be tonotopically organized. In this study, we used antidromic stimulation combined with other electrophysiological techniques to further investigate the spatial organization of descending fibers from A1 to the ICC in ketamine-anesthetized guinea pigs. Based on our findings, corticofugal fibers originate predominantly from layer V of A1, are amply scattered throughout the ICC and only project to ICC neurons with a similar best frequency (BF). This strict tonotopic pattern suggests that these corticofugal projections are involved with modulating spectral features of sound. Along the isofrequency dimension of the ICC, there appears to be some differences in projection patterns that depend on BF region and possibly isofrequency location within A1 and may be indicative of different descending coding strategies. Furthermore, the success of the antidromic stimulation method in our study demonstrates that it can be used to investigate some of the functional properties associated with corticofugal projections to the ICC as well as to other regions (e.g., medial geniculate body, cochlear nucleus). Such a method can address some of the limitations with current anatomical techniques for studying the auditory corticofugal system.

Convergence of spinal trigeminal and cochlear nucleus projections in the inferior colliculus of the guinea pig

In addition to ascending auditory inputs, the external cortex of the inferior colliculus (ICX) receives prominent somatosensory inputs. To elucidate the extent of interaction between auditory and somatosensory representations at the level of IC, we explored the dual projections from the cochlear nucleus (CN) and the spinal trigeminal nucleus (Sp5) to the inferior colliculus (IC) in the guinea pig, using both retrograde and anterograde tracing techniques. Injections of retrograde tracers into ICX resulted in cell-labeling primarily in the contralateral DCN and pars interpolaris and caudalis of Sp5. Labeled cells in DCN were either fusiform or multipolar cells, whereas those in Sp5 varied in size and shape. Injections of anterograde tracers into either CN or Sp5 resulted in terminal labeling in ICX primarily on the contralateral side. Most projection fibers from Sp5 terminated in a laminar pattern from ventromedial to dorsolateral within the ventrolateral ICX, the ventral border of IC, and the ventromedial edge of IC (collectively termed "the ventrolateral border region of IC," ICXV). Less dense anterograde labeling was observed in lateral and rostral ICX. Injecting different tracers into both Sp5 and CN confirmed the overlapping areas of convergent projections from Sp5 and CN in IC: The most intense dual labeling was seen in the ICXV, and less intense dual labeling was also observed in the rostral part of ICX. This convergence of projection fibers from CN and Sp5 provides an anatomical substrate for multimodal integration in the IC.

EVALUATION OF AUDITORY EVOKED POTENTIALS FROM THE INFERIOR COLLICULUS IN RAT

This study aimed to investigate the usefulness of auditory evoked potentials (AEPs) in rats. To this end, N1, P2 latencies, and the N1 P2 amplitude of responses to different acoustic stimuli from rats, which were implanted with permanent electrodes in the inferior colliculus (IC), were evaluated and used to demonstrate the frequency characteristics of IC region. Permanent electrodes were implanted in IC regions of 7 male albino rats by the stereotaxic method. The animals were exposed to five tones series of stimuli (1000 Hz, 2000 Hz, 4000 Hz, 6000 Hz, and 8000 Hz tones with 1500 ms interstimulus intervals) of 70 dB with a duration of 1000 ms. AEPs)were recorded and analyzed with the Brain-Data Acquisition system. There were no statistically significant differences in N1, P2 latencies, and the N1-P2 amplitude of AEPs from IC regions of rats as a result of changes in the frequency of stimulus. It was determined that the dominant frequency activity of the IC to acoustic stimulus was theta-alpha band, with theta as the peak frequency. As a result it was concluded that there are similarities between the N1, P2 components of rat AEPs, and human AEPs. We have suggested that the rats may provide a useful model for investigating the generation of middle latency components of AEPs in humans.