Burst discharges in neurons of the thalamic reticular nucleus are shaped by calcium-induced calcium release

Cell Calcium. 2009 Nov-Dec;46(5-6):333-46. doi: 10.1016/j.ceca.2009.09.005. Epub 2009 Nov 14.

Abstract

The nucleus reticularis thalami (NRT) is a layer of inhibitory neurons that surrounds the dorsal thalamus. It appears to be the 'pacemaker' of certain forms of slow oscillations in the thalamus and was proposed to be a key determinant of the internal attentional searchlight as well as the origin of hypersynchronous activity during absence seizures. Neurons of the NRT exhibit a transient depolarization termed low threshold spike (LTS) following sustained hyperpolarization. This is caused by the activation of low-voltage-activated Ca2+ channels (LVACC). Although the role of these channels in thalamocortical oscillations was studied in great detail, little is known about the downstream intracellular Ca2+ signalling pathways and their feedback onto the oscillations. A signalling triad consisting of the sarco(endo)plasmic reticulum calcium ATPase (SERCA), Ca2+ activated K+ channels (SK2), and LVACC is active in dendrites of NRT neurons and shapes rhythmic oscillations. The aim of our study was to find out (i) if and how Ca2+-induced Ca2+ release (CICR) via ryanodine receptors (RyR) can be evoked in NRT neurons and (ii) how the released Ca2+ affects burst activity. Combining electrophysiological, immunohistochemical, and two-photon Ca2+ imaging techniques, we show that CICR in NRT neurons takes place by a cell-type specific coupling of LVACC and RyR. CICR could be evoked by the application of caffeine, by activation of LVACC, or by repetitive LTS generation. During the latter, CICR contributed 30% to the resulting build-up of [Ca2+]i. CICR was abolished by cyclopiazonic acid, a specific blocker for SERCA, or by high concentrations of ryanodine (50 microM). Unlike other thalamic nuclei, in the NRT the activation of high-voltage-activated Ca2+ channels failed to evoke CICR. While action potentials contributed little to the build-up of [Ca2+]i upon repetitive LTS generation, the Ca2+ released via RyR significantly reduced the number of action potentials during an LTS and reduced the neurons' low threshold activity, thus potentially reducing hypersynchronicity. This effect persisted in the presence of the SK2 channel blocker apamin. We conclude that the activation of LVACC specifically causes CICR via RyR in neurons of the NRT, thereby adding a Ca2+-dependent intracellular route to the mechanisms determining rhythmic oscillatory bursting in this nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Apamin / pharmacology
  • Caffeine / pharmacology
  • Calcium / physiology*
  • Calcium Channels, T-Type / physiology*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Enzyme Inhibitors
  • In Vitro Techniques
  • Indoles / pharmacology
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Organ Specificity
  • Rats
  • Ryanodine / pharmacology
  • Ryanodine Receptor Calcium Release Channel / physiology*
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / antagonists & inhibitors
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / physiology*
  • Small-Conductance Calcium-Activated Potassium Channels / antagonists & inhibitors
  • Small-Conductance Calcium-Activated Potassium Channels / physiology
  • Thalamic Nuclei*

Substances

  • Calcium Channels, T-Type
  • Enzyme Inhibitors
  • Indoles
  • Ryanodine Receptor Calcium Release Channel
  • Small-Conductance Calcium-Activated Potassium Channels
  • Ryanodine
  • Apamin
  • Caffeine
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium
  • cyclopiazonic acid