No abstract

The present study suggests that the neural computations used to integrate information from different senses are distinct from those used to integrate information from within the same sense. Using superior colliculus neurons as a model, it was found that multisensory integration of cross-modal stimulus combinations yielded responses that were significantly greater than those evoked by the best component stimulus. In contrast, unisensory integration of within-modal stimulus pairs yielded responses that were similar to or less than those evoked by the best component stimulus. This difference is exemplified by the disproportionate representations of superadditive responses during multisensory integration and the predominance of subadditive responses during unisensory integration. These observations suggest that different rules have evolved for integrating sensory information, one (unisensory) reflecting the inherent characteristics of the individual sense and, the other (multisensory), unique supramodal characteristics designed to enhance the salience of the initiating event.

Converging cortical influences from the anterior ectosylvian sulcus and the rostral lateral suprasylvian sulcus were shown to have a multisensory-specific role in the integration of sensory information in superior colliculus (SC) neurons. These observations were based on changes induced by cryogenic deactivation of these cortico-SC projections. Thus, although the results indicated that they played a critical role in integrating SC responses to stimuli derived from different senses (i.e., visual-auditory), they played no role in synthesizing its responses to stimuli derived from within the same sense (visual-visual). This was evident even in the same multisensory neurons. The results suggest that very different neural circuits have evolved to code combinations of cross-modal and within-modal stimuli in the SC, and that the differences in multisensory and unisensory integration are likely caused by differences in the configuration of each neuron's functional inputs rather than to any inherent differences among the neurons themselves. The specificity of these descending influences was also apparent in the very different ways in which they affected responses to the component cross-modal stimuli and their actual integration. Furthermore, they appeared to target only multisensory neurons and not their unisensory neighbors.

Age-related hearing loss (ARHL) is one of the most frequent sensory impairments in senescence and is a source of important socio-economic consequences. Understanding the pathological responses that occur in the central auditory pathway of patients who suffer from this disability is vital to improve its diagnosis and treatment. Therefore, the goal of this study was to characterize age-related modifications in auditory brainstem responses (ABR) and to determine whether these functional responses might be accompanied by an imbalance between excitation and inhibition in the cochlear nucleus of Wistar rats. To do so, ABR recordings at different frequencies and immunohistochemistry for the vesicular glutamate transporter 1 (VGLUT1) and the vesicular GABA transporter (VGAT) in the ventral cochlear nucleus (VCN) were performed in young, middle-aged and old male Wistar rats. The results demonstrate that there was a significant increase in the auditory thresholds, a significant decrease in the amplitudes and an increase in the latencies of the ABR waves as the age of the rat increased. Additionally, there were decreases in VGLUT1 and VGAT immunostaining in the VCN of older rats compared to younger rats. Therefore, the observed age-related decline in the magnitude of auditory evoked responses might be due in part to a reduction in markers of excitatory function; meanwhile, the concomitant reduction in both excitatory and inhibitory markers might reflect a common central alteration in animal models of ARLH. Together, these findings highlight the suitability of the Wistar rat as an excellent model to study ARHL.

Repeated noise exposure induces inflammation and cellular adaptations in the peripheral and central auditory system resulting in pathophysiology of hearing loss. In this study, we analyzed the mechanisms by which noise-induced inflammatory-related events in the cochlea activate glial-mediated cellular responses in the cochlear nucleus (CN), the first relay station of the auditory pathway. The auditory function, glial activation, modifications in gene expression and protein levels of inflammatory mediators and ultrastructural changes in glial-neuronal interactions were assessed in rats exposed to broadband noise (0.5–32 kHz, 118 dB SPL) for 4 h/day during 4 consecutive days to induce long-lasting hearing damage. Noise-exposed rats developed a permanent threshold shift which was associated with hair cell loss and reactive glia. Noise-induced microglial activation peaked in the cochlea between 1 and 10D post-lesion; their activation in the CN was more prolonged reaching maximum levels at 30D post-exposure. RT-PCR analyses of inflammatory-related genes expression in the cochlea demonstrated significant increases in the mRNA expression levels of pro- and anti-inflammatory cytokines, inducible nitric oxide synthase, intercellular adhesion molecule and tissue inhibitor of metalloproteinase-1 at 1 and 10D post-exposure. In noise-exposed cochleae, interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α) were upregulated by reactive microglia, fibrocytes, and neurons at all time points examined. In the CN, however, neurons were the sole source of these cytokines. These observations suggest that noise exposure causes peripheral and central inflammatory reactions in which TNF-α and IL-1β are implicated in regulating the initiation and progression of noise-induced hearing loss.

Influences from the visual (AEV), auditory (FAES), and somatosensory (SIV) divisions of the cat anterior ectosylvian sulcus (AES) play a critical role in rendering superior colliculus (SC) neurons capable of multisensory integration. However, it is not known whether this is accomplished via their independent sensory-specific action or via some cross-modal cooperative action that emerges as a consequence of their convergence on SC neurons. Using visual-auditory SC neurons as a model, we examined how selective and combined deactivation of FAES and AEV affected SC multisensory (visual-auditory) and unisensory (visual-visual) integration capabilities. As noted earlier, multisensory integration yielded SC responses that were significantly greater than those evoked by the most effective individual component stimulus. This multisensory "response enhancement" was more evident when the component stimuli were weakly effective. Conversely, unisensory integration was dominated by the lack of response enhancement. During cryogenic deactivation of FAES and/or AEV, the unisensory responses of SC neurons were only modestly affected; however, their multisensory response enhancement showed a significant downward shift and was eliminated. The shift was similar in magnitude for deactivation of either AES subregion and, in general, only marginally greater when both were deactivated simultaneously. These data reveal that SC multisensory integration is dependent on the cooperative action of distinct subsets of unisensory corticofugal afferents, afferents whose sensory combination matches the multisensory profile of their midbrain target neurons, and whose functional synergy is specific to rendering SC neurons capable of synthesizing information from those particular senses.

The removal of afferent activity has been reported to modify neuronal activity in the cochlear nucleus of adult rats. After cell damage, microglial cells are rapidly activated, initiating a series of cellular responses that influences neuronal function and survival. To investigate how this glial response occurs and how it might influence injured neurons, bilateral cochlear ablations were performed on adult rats to examine the short-term (16 and 24 hours and 4 and 7 days) and long-term (15, 30, and 100 days) changes in the distribution and morphology of microglial cells (immunostained with the ionized calcium-binding adaptor molecule 1; Iba-1) and the interaction of microglial cells with deafferented neurons in the ventral cochlear nucleus. A significant increase in the mean cross-sectional area and Iba-1 immunostaining of microglial cells in the cochlear nucleus was observed at all survival times after the ablation compared with control animals. These increases were concomitant with an increase in the area of Iba-1 immunostaining at 24 hours and 4, 7, and 15 days postablation. Additionally, microglial cells were frequently seen apposing the cell bodies and dendrites of auditory neurons at 7, 15, and 30 days postablation. In summary, these results provide evidence for persistent glial activation in the ventral cochlear nucleus and suggest that long-term interaction occurs between microglial cells and deafferented cochlear nucleus neurons following bilateral cochlear ablation, which could facilitate the remodeling of the affected neuronal circuits.

In this study, we used image analysis to assess changes in calretinin immunoreactivity in the lateral (LSO) and medial (MSO) superior olivary nuclei in ferrets 2 months after unilateral cochlear ablations at 30-40 days of age, soon after hearing onset. These two nuclei are the first significant sites of binaural convergence in the ascending auditory system, and both receive direct projections from the deafferented cochlear nucleus. Cochlear ablation results in a decrease in the overall level of calretinin immunostaining within the LSO ipsilaterally compared with the contralateral side and with control animals and within the MSO bilaterally compared with control ferrets. In addition, the level of calretinin immunostaining ipsilaterally within neurons in the LSO was significantly less in cochlear ablated than control animals. In contrast, there was no effect of cochlear ablation on the level of calretinin immunostaining within neurons either in the contralateral LSO or in the MSO. These results are consistent with a downregulation in calretinin within the neuropil of MSO bilaterally and LSO ipsilaterally, as well as a downregulation in calretinin within somata in the ipsilateral LSO as a result of unilateral cochlear ablation soon after hearing onset. Thus, cochlear-driven activity appears to affect calcium binding protein levels in both neuropil and neurons within the superior olivary complex.