We have demonstrated that the trigeminal ganglion sends a projection to the auditory brain stem and to the cochlear vasculature. The terminations in the brainstem end in granular and magnocellular regions of the ventral cochlear nucleus (VCN) and at the locations of olivocochlear neurons in the superior olivary complex. The cochlear portion of the innervation modulates blood flow within the cochlea. However, the function of the brainstem projection is unknown. Preliminary findings suggest that the projection to the VCN is excitatory. The axons of granule' cells (parallel fibers) project to the dorsal cochlear nucleus (DCN). Therefore, excitation by the trigeminal innervation could affect most of the output neurons of the cochlear nucleus (CN). A series of studies is designed to elucidate the function of the CN portion of this new projection and define its neurotransmitters: The trigeminal ganglion will be electrically stimulated while observing the responses of single units in the CN. The candidate neurotransmitters, Substance P and Nitric Oxide, will be evaluated using immunocytochemistry and neuropharmacology. A role for the trigeminal ganglion in the generation and modulation of tinnitus will be explored: As many as two thirds of tinnitus patients are able modulate their tinnitus by clenching the jaw or touching the skin on the face, areas innervated by the trigeminal ganglion. Others can attribute the onset of tinnitus to a somatic insult in the head and neck region (""""""""somatic tinnitus""""""""). On the assumption that increased spontaneous rate is a manifestation of tinnitus, its modulation by somatosensory input to the CN could play a role in the generation and modulation of tinnitus. The hypothesis wifi be tested by electrically stimulating the trigeminal ganglion while recording spontaneous activity in single units of the CN. Identifying the neurotransmitter used in this pathway could then set the stage for later drug treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004825-04
Application #
6725386
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Luethke, Lynn E
Project Start
2001-04-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
4
Fiscal Year
2004
Total Cost
$263,298
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
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
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
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

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