The dorsal cochlear nucleus (DCN) integrates auditory and somatosensory information through circuitry that modulates activity of the principal output neurons of the circuit, the fusiform cells. Fusiform cells receive somatosensory information via synapses on their apical dendrites and acoustic information via their basal dendrites. When somatosensory activation is combined with sound, the circuit can be strengthened or weakened depending on the order of the bimodal stimuli. This process is called stimulus timing dependent plasticity. In the condition of phantom sound perception, or tinnitus, the DCN circuitry is strengthened to increase the firing rates and synchrony of fusiform cells. This proposal seeks to investigate the effects of manipulations on the circuitry of this first auditory brainstem nucleus by implementing a bimodal sound + electrical stimulus paradigm to alter the circuit in normal and pathological conditions. Animal and human studies will be conducted to optimize the stimulation parameters/dosages necessary to weaken the circuit and thus ameliorate the pathological condition. This will ultimately lead to treatments for neural disorders involving hyperactive or hyper synchronous circuits such as those identified for tinnitus or Parkinson's disease.
This proposed study will investigate non-invasive modulation of a specific circuit in the first central auditory system station, the dorsal cochlear nucleus. This circuit has previously been shown to become hyper- synchronized during pathology and is amenable to long term alterations through non-invasive stimulation using combined auditory and trans-dermal somatosensory stimulation. Here, we will examine dose response of this stimulation by varying the duration and stimulus intervals of bimodal stimulation in animals and humans. Outcome measures will include measuring tinnitus, which is one pathological outcome of hyper-synchronized circuits, but could also be applied to other conditions such as central motor disorders.
|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|
|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:|