| Affiliation: | 1. Translational Brain Research Center, Catholic Kwandong University International St. Mary''s Hospital, Incheon, South Korea;2. Dept. of Medical Science, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, South Korea;3. Department of Neuroscience, University of Science and Technology, Daejeon, South Korea;4. Department of Electrical and Computer Engineering, Seoul National University, Seoul, South Korea;5. Center for Neuroscience, Korea Institute of Science and Technology, Seoul, South Korea;6. Department of Biomedical Engineering, The City College of the City University of New York, NY, USA;7. Department of Radiology, Incheon St. Mary''s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea;8. Department of Psychology, University of Washington, Seattle, WA, USA |
| Abstract: | BackgroundThe bursting pattern of thalamocortical (TC) pathway dampens nociception. Whether brain stimulation mimicking endogenous patterns can engage similar sensory gating processes in the cortex and reduce nociceptive behaviors remains uninvestigated.ObjectiveWe investigated the role of cortical parvalbumin expressing (PV) interneurons within the TC circuit in gating nociception and their selective response to TC burst patterns. We then tested if transcranial magnetic stimulation (TMS) patterned on endogenous nociceptive TC bursting modulate nociceptive behaviors.MethodsThe switching of TC neurons between tonic (single spike) and burst (high frequency spikes) firing modes may be a critical component in modulating nociceptive signals. Deep brain electrical stimulation of TC neurons and immunohistochemistry were used to examine the differential influence of each firing mode on cortical PV interneuron activity. Optogenetic stimulation of cortical PV interneurons assessed a direct role in nociceptive modulation. A new TMS protocol mimicking thalamic burst firing patterns, contrasted with conventional continuous and intermittent theta burst protocols, tested if TMS patterned on endogenous TC activity reduces nociceptive behaviors in mice.ResultsImmunohistochemical evidence confirmed that burst, but not tonic, deep brain stimulation of TC neurons increased the activity of PV interneurons in the cortex. Both optogenetic activation of PV interneurons and TMS protocol mimicking thalamic burst reduced nociceptive behaviors.ConclusionsOur findings suggest that burst firing of TC neurons recruits PV interneurons in the cortex to reduce nociceptive behaviors and that neuromodulation mimicking thalamic burst firing may be useful for modulating nociception. |
