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

Brain Structure and Function - Tập 220 - Trang 3023-3041 - 2014
Áron Kőszeghy1, Adrienn Kovács1, Tamás Bíró1,2, Péter Szücs1,3, János Vincze1, Zoltán Hegyi4, Miklós Antal4,5, Balázs Pál1
1Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
2“DE-MTA Lendület” Cellular Physiology Research Group of the Hungarian Academy of Sciences, Debrecen, Hungary
3MTA-DE-NAP B-Pain Control Research Group, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
4Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
5MTA-DE Neuroscience Research Group, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

Tóm tắt

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.

Tài liệu tham khảo

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