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Temporal coding of auditory stimuli is critical for understanding communication signals. The bushy cell, a major output neuron of the ventral cochlear nucleus, can "phase-lock" precisely to pure tones and the envelopes of complex stimuli. Bushy cells are also putative recipients of brainstem somatosensory projections and could therefore play a role in perception of communication signals because multisensory integration is required for such complex sound processing. Here, we examine the role of multisensory integration in temporal coding in bushy cells by activating the spinal trigeminal nucleus (Sp5) while recording responses from bushy cells. In normal-hearing guinea pigs of either sex, bushy cell single unit responses to amplitude-modulated (AM) broadband noise were compared with those in the presence of preceding Sp5 electrical stimulation (i.e., bimodal stimuli). Responses to the AM stimuli were also compared with those obtained 45 min after the bimodal stimulation. Bimodal auditory-Sp5 stimulation resulted in enhanced envelope coding for low modulation frequencies, which persisted for up to 45 min. AM detection thresholds were significantly improved 45 min after bimodal auditory-Sp5 stimulation, but not during bimodal auditory-Sp5 stimulation. Anterograde labeling of Sp5 projections was found within the dendritic fields of bushy cells and their inhibitory interneurons, D-stellate cells. Therefore, enhanced AM responses and improved AM sensitivity of bushy cells were likely facilitated by Sp5 neurons through monosynaptic excitatory projections and indirect inhibitory projections. These somatosensory projections may be involved in the improved perception of communication stimuli with multisensory stimulation, consistent with psychophysical studies in humans. [ABSTRACT FROM AUTHOR]

Tinnitus, the perception of phantom sounds, is thought to arise from increased neural synchrony, which facilitates perceptual binding and creates salient sensory features in the absence of physical stimuli. In the auditory cortex, increased spontaneous cross-unit synchrony and single-unit bursting are de facto physiological correlates of tinnitus. However, it is unknown whether neurons in the dorsal cochlear nucleus (DCN), the putative tinnitus-induction site, exhibit increased synchrony. Using a temporary-threshold shift model and gap-prepulse inhibition of the acoustic startle to assess tinnitus, we recorded spontaneous activity from fusiform cells, the principle neurons of the DCN, in normal hearing, tinnitus, and non-tinnitus guinea pigs. Synchrony and bursting, as well as spontaneous firing rate (SFR), correlated with behavioral evidence of tinnitus, and increased synchrony and bursting were associated with SFR elevation. The presence of increased synchrony and bursting in DCN fusiform cells suggests that a neural code for phantom sounds emerges in this brainstem location and likely contributes to the formation of the tinnitus percept. [ABSTRACT FROM AUTHOR]

Tinnitus and cochlear damage have been associated with changes in somatosensory-auditory integration and plasticity in the dorsal cochlear nucleus (DCN). Recently, we demonstrated in vivo that DCN bimodal plasticity is stimulus timing-dependent, with Hebbian and anti-Hebbian timing rules that reflect in vitro spike timing-dependent plasticity. In this in vivo study, we assessed the stimulus timing dependence of bimodal plasticity in a tinnitus model. Guinea pigs were exposed to a narrowband noise that produced a temporary elevation of auditory brainstem response thresholds. A total of 60% of the guinea pigs developed tinnitus as indicated by gap-induced prepulse inhibition of the acoustic startle. After noise exposure and tinnitus induction, stimulus timing-dependent plasticity was mea-sured by comparing responses to sound before and after paired somatosensory and auditory stimulation presented with varying intervals and orders. In comparison with Sham and noise-exposed animals that did not develop tinnitus, timing rules in verified tinnitus animals were more likely to be anti-Hebbian and broader for those bimodal intervals in which the neural activity showed enhancement. Further-more, units from exposed animals with tinnitus were more weakly suppressed than either Sham animals or exposed animals without tinnitus. The broadened timing rules in the enhancement phase in animals with tinnitus, and in the suppressive phase in exposed animals without tinnitus was in contrast to narrow, Hebbian-like timing rules in Sham animals. These findings implicate alterations in DCN bimodal spike timing-dependent plasticity as underlying mechanisms in tinnitus, opening the way for a therapeutic target. [ABSTRACT FROM AUTHOR]

The cochlear nucleus (CN) receives innervation from auditory and somatosensory structures, which can be identified using vesicular glutamate transporters, VGLUT1 and VGLUT2. VGLUT1 is highly expressed in the magnocellular ventral CN (VCN), which receives auditory nerve inputs. VGLUT2 is predominantly expressed in the granule cell domain (GCD), which receives nonauditory inputs from somatosensory nuclei, including spinal trigeminal nucleus (Sp5) and cuneate nucleus (Cu). Two weeks after unilateral deafening VGLUT1 is significantly decreased in ipsilateral VCN while VGLUT2 is significantly increased in the ipsilateral GCD (Zeng et al., 2009), putatively reflecting decreased inputs from auditory nerve and increased inputs from nonauditory structures in guinea pigs. Here, we wished to determine whether the upregulation of VGLUT2 represents increases in the number of somatosensory projections to the CN that are maintained for longer periods of time. Thus, we examined concurrent changes in VGLUT levels and somatosensory projections in the CN using immunohistochemistry combined with anterograde tract tracing three and six weeks following unilateral deafening. The data reveal that unilateral deafness leads to increased numbers of VGLUT2-colabeled Sp5 and Cu projections to the ventral and dorsal CN. These findings suggest that Sp5 and Cu play significant and unique roles in cross-modal compensation and that, unlike after shorter term deafness, neurons in the magnocellular regions also participate in the compensation. The enhanced glutamatergic somatosensory projections to the CN may play a role in neural spontaneous hyperactivity associated with tinnitus. [ABSTRACT FROM AUTHOR]

The dorsal cochlear nucleus (DCN) is the first neural site of bimodal auditory-somatosensory integration. Previous studies have shown that stimulation of somatosensory pathways results in immediate suppression or enhancement of subsequent acoustically evoked discharges. In the unimpaired auditory system suppression predominates. However, damage to the auditory input pathway leads to enhancement of excitatory somatosensory inputs to the cochlear nucleus, changing their effects on DCN neurons (Shore et al., 2008; Zeng et al., 2009). Given the well described connection between the somatosensory system and tinnitus in patients we sought to determine whether plastic changes in long-lasting bimodal somatosensory-auditory processing accompany tinnitus. Here we demonstrate for the first time in vivo long-term effects of somatosensory inputs on acoustically evoked discharges of DCN neurons in guinea pigs. The effects of trigeminal nucleus stimulation are compared between normal-hearing animals and animals overexposed with narrow band noise and behaviorally tested for tinnitus. The noise exposure resulted in a temporary threshold shift in auditory brainstem responses but a persistent increase in spontaneous and sound-evoked DCN unit firing rates and increased steepness of rate-level functions. Rate increases were especially prominent in buildup units. The long-term somatosensory enhancement of sound-evoked responses was strengthened while suppressive effects diminished in noise-exposed animals, especially those that developed tinnitus. Damage to the auditory nerve is postulated to trigger compensatory long-term synaptic plasticity of somatosensory inputs that might be an important underlying mechanism for tinnitus generation. [ABSTRACT FROM AUTHOR]

Tinnitus is a phantom sound (ringing of the ears) that affects quality of life for millions around the world and is associated in most cases with hearing impairment. This symposium will consider evidence that deafferentation of tonotopically organized central auditory structures leads to increased neuron spontaneous firing rates and neural synchrony in the hearing loss region. This region covers the frequency spectrum of tinnitus sounds, which are optimally suppressed following exposure to band-limited noise covering the same frequencies. Cross-modal compensations in subcortical structures may contribute to tinnitus and its modulation by jaw-clenching and eye movements. Yet many older individuals with impaired hearing do not have tinnitus, possibly because age-related changes in inhibitory circuits are better preserved.Abrain network involving limbic and other nonauditory regions is active in tinnitus and may be driven when spectrotemporal information conveyed by the damaged ear does not match that predicted by central auditory processing. [ABSTRACT FROM AUTHOR]

Integration of multimodal information is essential for understanding complex environments. In the auditory system, multisensory integration first occurs in the cochlear nucleus (CN), where auditory nerve and somatosensory pathways converge (Shore, 2005). A unique feature of multisensory neurons is their propensity to receive cross-modal compensation after deafening. Based on our findings that the vesicular glutamate transporters, VGLUT1 and VGLUT2, are differentially associated with auditory nerve and somatosensory inputs to the CN, respectively (Zhou et al., 2007), we examined their relative distributions after unilateral deafening. After unilateral intracochlear injections of kanamycin (1 and 2 weeks), VGLUT1 immunoreactivity (ir) in the magnocellular CN ipsilateral to the cochlear damage was significantly decreased, whereas VGLUT2-ir in regions that receive nonauditory input was significantly increased 2 weeks after deafening. The pathway-specific amplification of VGLUT2 expression in the CN suggests that, in compensatory response to deafening, the nonauditory influence on CN is significantly enhanced. One undesirable consequence of enhanced glutamatergic inputs could be the increased spontaneous rates in CN neurons that occur after hearing loss and that have been proposed as correlates of the phantom auditory sensations commonly called tinnitus. [ABSTRACT FROM AUTHOR]