The long term goal of this research program is to elucidate both the normal role of non-auditory inputs to the cochlear nucleus (CN), and how alterations of these inputs after deafness may lead to a re-organization of bimodal interactions that result in the perception of phantom sounds or tinnitus. A significant finding from this funding period is that stimulating trigeminal neurons can dramatically suppress acoustically driven responses in dorsal CN (DCN) units. This suggests that somatosensory- auditory integration may be involved in the suppression of internally-generated sounds such as self vocalization or respiration. Investigating the mechanisms underlying this bimodal integration will allow us to appreciate the role of the DCN in improving the detection of external, novel stimuli.
Aim 1 will describe the projections from the spinal trigeminal nucleus (Sp5) and lateral reticular formation (RF) to the CN. Electrically stimulating these regions will enable us to learn more about their contributions to auditory processing within the DCN.
Aim two will determine the mechanisms underlying bimodal integration in the DCN. The hypotheses invoked to explain the long lasting integration include long term depression/potentiation, transient potassium channel activation, or GABAB receptor activation. These hypotheseswill be tested using multichannel recording probes, enabling us to record simultaneously from a large number of units. The focus will be on the changes in temporal firing patterns of DCN units in response to trigeminal stimulation.
Aim three will explore our recent observation that DCN units become more sensitive to trigeminal stimulation after cochlear damage: Changes in the temporal firing patterns of DCN units may reflect altered intrinsic membrane properties or an increase in the number of trigeminal inputs following cochlear damage. The hypothesis that trigeminal innervation may increase following noise damage will be investigated using vesicular glutamate and GAP-43/synaptophysin/synapsin1 immuno cytochemistry combined with tract tracing. Increased synchrony between neurons may be a correlate of tinnitus and changes in regularity and synchrony with trigeminal stimulation may be a correlate of somatic tinnitus. Thus, examining the disruption of bimodal integration following cochlear damage will allow us to elucidate the mechanisms underlying tinnitus, and thus provide insights to guide clinical intervention.
|Heeringa, Amarins N; Wu, Calvin; Shore, Susan E (2018) Multisensory Integration Enhances Temporal Coding in Ventral Cochlear Nucleus Bushy Cells. J Neurosci 38:2832-2843|
|Marks, Kendra L; Martel, David T; Wu, Calvin et al. (2018) Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans. Sci Transl Med 10:|
|Martel, David T; Pardo-Garcia, Thibaut R; Shore, Susan E (2018) Dorsal Cochlear Nucleus Fusiform-cell Plasticity is Altered in Salicylate-induced Tinnitus. Neuroscience :|
|Heeringa, Amarins N; Wu, Calvin; Chung, Christopher et al. (2018) Glutamatergic Projections to the Cochlear Nucleus are Redistributed in Tinnitus. Neuroscience 391:91-103|
|Stefanescu, Roxana A; Shore, Susan E (2017) Muscarinic acetylcholine receptors control baseline activity and Hebbian stimulus timing-dependent plasticity in fusiform cells of the dorsal cochlear nucleus. J Neurophysiol 117:1229-1238|
|Heeringa, A N; Stefanescu, R A; Raphael, Y et al. (2016) Altered vesicular glutamate transporter distributions in the mouse cochlear nucleus following cochlear insult. Neuroscience 315:114-24|
|Wu, Calvin; Stefanescu, Roxana A; Martel, David T et al. (2016) Tinnitus: Maladaptive auditory-somatosensory plasticity. Hear Res 334:20-9|
|Kurioka, Takaomi; Lee, Min Young; Heeringa, Amarins N et al. (2016) Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus. Neuroscience 332:242-57|
|Wu, Calvin; Martel, David T; Shore, Susan E (2016) Increased Synchrony and Bursting of Dorsal Cochlear Nucleus Fusiform Cells Correlate with Tinnitus. J Neurosci 36:2068-73|
|Shore, Susan E; Roberts, Larry E; Langguth, Berthold (2016) Maladaptive plasticity in tinnitus--triggers, mechanisms and treatment. Nat Rev Neurol 12:150-60|
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