Auditory-Somatosensory Integration in Dorsal Cochlear Nucleus Mediates Normal and Phantom Sound Perception.

[摘要] The dorsal cochlear nucleus (DCN) is the first auditory brainstem nucleus that processes and relays sensory information from multiple sensory modalities to higher auditory brain structures. Converging somatosensory and auditory inputs are integrated by bimodal DCN fusiform neurons, which use somatosensory context for improved auditory coding. Furthermore, phantom sound perception, or tinnitus, can be modulated or induced by somatosensory stimuli including facial pressure and has been linked to somatosensory-auditory processing in DCN. I present three in vivo neurophysiology studies in guinea pigs investigating the role of multisensory mechanisms in normal and tinnitus models.1) DCN fusiform cells respond to sound with characteristic spike-timing patterns that are controlled by rapidly inactivating potassium conductances. I demonstrated here that somatosensory stimulation alters sound-evoked firing rates and temporal representations of sound for tens of milliseconds through synaptic modulation of intrinsic excitability. 2) Bimodal plasticity consists of alterations of sound-evoked responses for up to two hours after paired somatosensory-auditory stimulation. By varying the interval and order between sound and somatosensory stimuli, I demonstrated stimulus-timing dependent bimodal plasticity that implicates spike-timing dependent synaptic plasticity (STDP) as the underlying mechanism. The timing rules and time course of stimulus-timing dependent plasticity closely mimic those of STDP at synapses conveying somatosensory information to the DCN. These results suggest the DCN performs STDP-dependent adaptive processing such as suppression of body-generated sounds.3) Finally, I assessed stimulus-timing dependence of bimodal plasticity in a tinnitus model. Guinea pigs were exposed to a narrowband noise that produced temporary shifts in auditory brainstem response thresholds and is known to produce tinnitus. Sixty percent of guinea pigs developed tinnitus according to behavioral testing by gap-induced prepulse inhibition of the acoustic startle response. Bimodal plasticity timing rules in animals with verified tinnitus were broader and more likely to be anti-Hebbian than those in sham animals or noise-exposed animals that did not develop tinnitus. Furthermore, exposed animals with tinnitus had weaker suppressive responses than either sham animals or exposed animals without tinnitus. These results suggest tinnitus development is linked to STDP, presenting a potential target for pharmacological or neuromodulatory tinnitus therapies.

[发布机构] University of Michigan

[效力级别] Multisensory

[关键词] Auditory System;Multisensory;Tinnitus;Plasticity;Spike-timing Dependent Plasticity;Dorsal Cochlear Nucleus;Biomedical Engineering;Physiology;Engineering;Science;Biomedical Engineering