caa a22 4500 606202897 CHVBK 20210128100955.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00429-014-0842-5 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0842-5 Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes [Elektronische Daten] [Áron Kőszeghy, Adrienn Kovács, Tamás Bíró, Péter Szücs, János Vincze, Zoltán Hegyi, Miklós Antal, Balázs Pál] 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. Springer-Verlag Berlin Heidelberg, 2014 Pedunculopontine nucleus nationallicence CB1 receptor nationallicence Neuromodulation nationallicence Astrocyte nationallicence Metabotropic glutamate receptor nationallicence Kőszeghy Áron Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary aut Kovács Adrienn Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary aut Bíró Tamás Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary aut Szücs Péter Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary aut Vincze János Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary aut Hegyi Zoltán Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary aut Antal Miklós Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary aut Pál Balázs Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary aut Brain Structure and Function Springer Berlin Heidelberg 220/5(2015-09-01), 3023-3041 1863-2653 220:5<3023 2015 220 429 https://doi.org/10.1007/s00429-014-0842-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0842-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kőszeghy Áron Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary aut NATIONALLICENCE 700 1- Kovács Adrienn Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary aut NATIONALLICENCE 700 1- Bíró Tamás Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary aut NATIONALLICENCE 700 1- Szücs Péter Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary aut NATIONALLICENCE 700 1- Vincze János Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary aut NATIONALLICENCE 700 1- Hegyi Zoltán Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary aut NATIONALLICENCE 700 1- Antal Miklós Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary aut NATIONALLICENCE 700 1- Pál Balázs Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/5(2015-09-01), 3023-3041 1863-2653 220:5<3023 2015 220 429