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 - 연자 : 김유신 교수(University of Alabama at Birmingham (UAB))
 - 제목 : Functional peripheral and central vagal neural circuits of interoception inhibiting pain
 - 일시 : 2026년 2월 9일(월) 오전11시
 - 장소 : 연구관 708호 회의실

Abstract:
Despite the clinical implications and decades of research, the molecular and cellular mechanisms underlying chronic pain remain unclear. Using a powerful in vivo TG (>2800 neurons/TG), dura mater, and DRG (>1800 neurons/DRG) GCaMP imaging approach, we have identified a striking neuronal circuit plasticity in the TG and other peripheral systems. A TG-related TMJ pain study with an interoception mechanism is developed using these tools and techniques. The vagus nerve is a primary conduit of interoceptive information, yet how specific vagal sensory afferents contribute to pain regulation remains poorly understood. Here, we investigated whether vagus nerve stimulation (VNS) modulates temporomandibular disorder (TMD)–related pain and identified the afferent populations underlying this effect. Using a mouse model of TMD, we show that auricular VNS (aVNS) robustly attenuates temporomandibular joint (TMJ) pain behaviors and suppresses trigeminal sensitization. We further identify a distinct subset of vagal sensory afferents that is sufficient to mediate these analgesic effects. Selective activation of these afferents originating from the TMJ region recapitulates the pain-relieving effects of aVNS. Together, our findings reveal a previously unrecognized interoceptive pathway through which defined vagal sensory afferents regulate trigeminal pain. This work establishes a cellular and mechanistic framework for precision neuromodulation strategies targeting chronic TMD-related craniofacial pain.

In vivo dynamic voltage and calcium imaging of primary sensory neurons in health and disease: Genetically-encoded voltage indicators (GEVIs) that reveal subthreshold electrical activity and resolve fast spike timing with subcellular resolution offer numerous advantages during in vivo potential imaging with high temporal resolution. Here, we used soma-targeted ASAP4, a novel GEVI, to dissect the temporal dynamics of noxious and non-noxious neuronal signals during mechanical, thermal, or chemical stimulation in the DRG of live mice. The ASAP4 is sufficiently bright and fast enough to characterize individual neuron coding dynamics, typically. Notably, using ASAP4, we uncovered cell-to-cell electrical synchronization between adjacent DRG neurons and robust dynamic transformations in sensory coding following tissue injury. We also developed pirt-Marina in vivo voltage imaging (Marina is a positively tuned voltage sensor), and the latest voltage sensor, pAce, a fluorescence resonance energy transfer (FRET)- based voltage sensor, has been developed in our lab. Finally, we found that combining GEVI and GECI GCaMP calcium imaging enabled in vivo optical studies of sensory signal processing and integration mechanisms with optimal spatiotemporal analysis.