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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004825-10
Application #
7993060
Study Section
Auditory System Study Section (AUD)
Program Officer
Miller, Roger
Project Start
2001-04-01
Project End
2012-02-29
Budget Start
2010-12-01
Budget End
2012-02-29
Support Year
10
Fiscal Year
2011
Total Cost
$304,333
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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; Stefanescu, Roxana A; Martel, David T et al. (2016) Tinnitus: Maladaptive auditory-somatosensory plasticity. Hear Res 334:20-9
Shore, Susan E; Roberts, Larry E; Langguth, Berthold (2016) Maladaptive plasticity in tinnitus--triggers, mechanisms and treatment. Nat Rev Neurol 12:150-60
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
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. (2015) Listening to another sense: somatosensory integration in the auditory system. Cell Tissue Res 361:233-50
Stefanescu, Roxana A; Koehler, Seth D; Shore, Susan E (2015) Stimulus-timing-dependent modifications of rate-level functions in animals with and without tinnitus. J Neurophysiol 113:956-70
Basura, Gregory J; Koehler, Seth D; Shore, Susan E (2015) Bimodal stimulus timing-dependent plasticity in primary auditory cortex is altered after noise exposure with and without tinnitus. J Neurophysiol 114:3064-75
Stefanescu, Roxana A; Shore, Susan E (2015) NMDA Receptors Mediate Stimulus-Timing-Dependent Plasticity and Neural Synchrony in the Dorsal Cochlear Nucleus. Front Neural Circuits 9:75
Wu, Calvin; Martel, David T; Shore, Susan E (2015) Transcutaneous induction of stimulus-timing-dependent plasticity in dorsal cochlear nucleus. Front Syst Neurosci 9:116

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