Jeiwon Cho, PhD
Translational Brain Research Center, Catholic Kwandong University International St. Mary’s Hospital, Incheon
Department of Medical Science, College of Medicine, Catholic Kwandong University, Gangneung

Pain Modulation Based on the Operational Mechanism of the Thalamocortical Circuit
Nociception serves vital protective functions against bodily injury. The thalamocortical (TC) pathway, which transmits sensory information to the cortex, is essential for perception of nociception. The thalamus is a structure extensively studied for its sensory gating role via the characteristic ability of a single thalamic neuron to switch between tonic (single spike) and burst (high frequency spikes) firing modes. However, how the respective firing modes contribute to nociceptive signal processing is unclear and the role of burst firing has been controversial. The current study attempted to uncover the role of thalamic burst firing in nociceptive signaling, in respect to the TC circuit, which is a tripartite circuitry composed of connections between the sensory thalamus, reticular thalamus, and the cortex. Single unit recordings of thalamic neurons in awake behaving mice suggested the importance of specific bursting in controlling nociceptive behavior. Subsequent thalamic electrical stimulation studies, that tested the various forms of bursts, confirmed that only thalamic burst stimulations with specific properties reduced formalin induced nociceptive behaviors. The anti-nociceptive effect of thalamic bursts were also found to occur in collaboration with a type of interneuron in the cortex. Immunohistochemical evidence showed that only burst stimulation which had an anti-nociceptive effect, but not tonic stimulation,
increased the activity of parvalbumin (PV) interneurons in the cortex. Using optogenetic techniques, we showed that selectively stimulated cortical PV interneurons reduced nociceptive behaviors. We then further investigated whether a non-invasive transcranial magnetic stimulation (TMS) patterned to mimic thalamic bursts could modulate nociceptive behaviors and confirmed that it could indeed reduce nociceptive behaviors in mice. Overall our study elucidates how nociceptive signals are processed in the TC circuit and suggest the importance of designing neuromodulation methods, e.g. TMS, based on the understanding of functional brain circuits.

This free lecture is made possible in part by a generous endowment from Professor Roger B. Loucks.