Tuning thalamic firing modes via simultaneous modulation of T- and L-type Ca2+ channels controls pain sensory gating in the thalamus

Eunji Cheong, Sukchan Lee, B. Jiwon Choi, Minjeong Sun, Changjoon Lee, Hee Sup Shin

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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 Cβ4 (PLCβ4) pathway, its molecular mechanisms have not been well elucidated. We addressed these questions using PLCβ4-deficient mice, which show decreased visceral pain responses. We demonstrate that burst and tonic firings of TC neurons are concomitantly regulated by PLCβ4 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 PLCβ4, 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 PLCβ4-PKC pathway as a "molecular switch" for the firing modes of TC neurons and thus for pain sensory gating.

Original languageEnglish
Pages (from-to)13331-13340
Number of pages10
JournalJournal of Neuroscience
Volume28
Issue number49
DOIs
Publication statusPublished - 2008 Dec 3
Externally publishedYes

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Keywords

  • Ca channels
  • Knock-out mice
  • Phospholipase Cβ4
  • Sensory gating
  • Thalamus
  • Visceral pain

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

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