Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes

Áron Kőszeghy, Adrienn Kovács, Tamás Bíró, Péter Szücs, János Vincze, Zoltán Hegyi, Miklós Antal, Balázs Pál

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The pedunculopontine nucleus (PPN) is known as the cholinergic part of the reticular activating system (RAS) and it plays an important role in transitions of slow-wave sleep to REM sleep and wakefulness. Although both exogenous and endocannabinoids affect sleep, the mechanism of endocannabinoid neuromodulation has not been characterized at cellular level in the PPN. In this paper, we demonstrate that both neurons and glial cells from the PPN respond to cannabinoid type 1 (CB1) receptor agonists. The neuronal response can be depolarization or hyperpolarization, while astrocytes exhibit more frequent calcium waves. All these effects are absent in CB1 gene-deficient mice. Blockade of the fast synaptic neurotransmission or neuronal action potential firing does not change the effect on the neuronal membrane potential significantly, while inhibition of astrocytic calcium waves by thapsigargin diminishes the response. Inhibition of group I metabotropic glutamate receptors (mGluRs) abolishes hyperpolarization, whereas blockade of group II mGluRs prevents depolarization. Initially active neurons and glial cells display weaker responses partially due to the increased endocannabinoid tone in their environment. Taken together, we propose that cannabinoid receptor stimulation modulates PPN neuronal activity in the following manner: active neurons may elicit calcium waves in astrocytes via endogenous CB1 receptor agonists. Astrocytes in turn release glutamate that activates different metabotropic glutamate receptors of neurons and modulate PPN neuronal activity.

Original languageEnglish
Pages (from-to)3023-3041
Number of pages19
JournalBrain Structure and Function
Volume220
Issue number5
DOIs
Publication statusPublished - Jul 10 2014

Fingerprint

Endocannabinoids
Astrocytes
Metabotropic Glutamate Receptors
Calcium Signaling
Cannabinoid Receptor Agonists
Neurons
Neuroglia
Sleep
Cannabinoid Receptors
Thapsigargin
Cannabinoids
Wakefulness
REM Sleep
Cell Nucleus
Synaptic Transmission
Membrane Potentials
Cholinergic Agents
Action Potentials
Glutamic Acid
Genes

Keywords

  • Astrocyte
  • CB1 receptor
  • Metabotropic glutamate receptor
  • Neuromodulation
  • Pedunculopontine nucleus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Anatomy
  • Histology

Cite this

Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes. / Kőszeghy, Áron; Kovács, Adrienn; Bíró, Tamás; Szücs, Péter; Vincze, János; Hegyi, Zoltán; Antal, Miklós; Pál, Balázs.

In: Brain Structure and Function, Vol. 220, No. 5, 10.07.2014, p. 3023-3041.

Research output: Contribution to journalArticle

Kőszeghy, Áron ; Kovács, Adrienn ; Bíró, Tamás ; Szücs, Péter ; Vincze, János ; Hegyi, Zoltán ; Antal, Miklós ; Pál, Balázs. / Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes. In: Brain Structure and Function. 2014 ; Vol. 220, No. 5. pp. 3023-3041.
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