Cheong, Eunji Lee, Sukchan Choi, B. Jiwon Sun, Minjeong Lee, C. Justin Shin, Hee-Sup 2024-01-20T22:05:00Z 2024-01-20T22:05:00Z 2021-09-03 2008-12-03 0270-6474 https://pubs.kist.re.kr/handle/201004/132884 Two firing modes of thalamocortical (TC) neurons, tonic and burst firings, are thought to reflect the divergent states of sensory signal transmission from the thalamus to the cortex. However, the behavioral consequences of changes in the thalamic firing between the two modes have not been well demonstrated. Moreover, although the firing modes of TC neurons are known to be affected by corticothalamic inputs via thalamic metabotropic glutamate receptor type 1 (mGluR1)-phospholipase C beta 4 (PLC beta 4) pathway, its molecular mechanisms have not been well elucidated. We addressed these questions using PLC beta 4-deficient mice, which show decreased visceral pain responses. We demonstrate that burst and tonic firings of TC neurons are concomitantly regulated by PLC beta 4 pathway. Blocking of this pathway by the mutation simultaneously increases bursting and decreases tonic firing of TC neurons through concurrent upregulation of T- and L-type Ca2+ currents. The mice with increased bursting and decreased tonic firing of TC neurons showed reduced visceral pain responses. Furthermore, we show that modulation of the Ca2+ channels or protein kinase C (PKC), a downstream molecule of PLC beta 4, altered the firing modes of TC neurons and pain responses in the predicted ways. Our data demonstrate the molecular mechanism and behavioral consequences of altered firing modes of TC neurons in relaying the visceral pain signals. Our study also highlights the thalamic PLC beta 4-PKC pathway as a "molecular switch" for the firing modes of TC neurons and thus for pain sensory gating. English SOC NEUROSCIENCE METABOTROPIC GLUTAMATE-RECEPTOR CA2+-ACTIVATED K+ CHANNELS LATERAL GENICULATE-NUCLEUS HIPPOCAMPAL-NEURONS CALCIUM-CHANNELS MICE LACKING SOMATOSENSORY CORTEX ABSENCE SEIZURES MESSENGER-RNA RELAY NEURONS Tuning Thalamic Firing Modes via Simultaneous Modulation of T- and L-Type Ca2+ Channels Controls Pain Sensory Gating in the Thalamus Article 10.1523/JNEUROSCI.3013-08.2008 1 JOURNAL OF NEUROSCIENCE, v.28, no.49, pp.13331 - 13340 JOURNAL OF NEUROSCIENCE 28 49 13331 13340 scie scopus 000261378100033 2-s2.0-58149378378 Neurosciences Neurosciences & Neurology Article METABOTROPIC GLUTAMATE-RECEPTOR CA2+-ACTIVATED K+ CHANNELS LATERAL GENICULATE-NUCLEUS HIPPOCAMPAL-NEURONS CALCIUM-CHANNELS MICE LACKING SOMATOSENSORY CORTEX ABSENCE SEIZURES MESSENGER-RNA RELAY NEURONS thalamus Ca2+ channels phospholipase C beta 4 visceral pain sensory gating knock-out mice