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

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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.

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References

  • Bezzi P, Gundersen V, Galbete JL, Seifert G, Steinhäuser C, Pilati E, Volterra A (2004) Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat Neurosci 7(6):613–620

    Article  CAS  PubMed  Google Scholar 

  • Bolla KI, Lesage SR, Gamaldo CE, Neubauer DN, Funderburk FR, Cadet JL, David PM, Verdejo-Garcia A, Benbrook AR (2008) Sleep disturbance in heavy marijuana users. Sleep 31(6):901–908

    PubMed Central  PubMed  Google Scholar 

  • Castillo PE, Younts TJ, Chávez AE, Hashimotodani Y (2012) Endocannabinoid signaling and synaptic function. Neuron 76(1):70–81

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chavis P, Shinozaki H, Bockaert J, Fagni L (1994) The metabotropic glutamate receptor types 2/3 inhibit L-type calcium channels via a pertussis toxin-sensitive G-protein in cultured cerebellar granule cells. J Neurosci 14(11 Pt 2):7067–7076

    CAS  PubMed  Google Scholar 

  • Chavis P, Fagni L, Bockaert J, Lansman JB (1995) Modulation of calcium channels by metabotropic glutamate receptors in cerebellar granule cells. Neuropharmacology 34(8):929–937

    Article  CAS  PubMed  Google Scholar 

  • Coiret G, Ster J, Grewe B, Wendling F, Helmchen F, Gerber U, Benquet P (2012) Neuron to astrocyte communication via cannabinoid receptors is necessary for sustained epileptiform activity in rat hippocampus. PLoS ONE 7(5):e37320

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cotrina ML, Lin JH, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, Kang J, Naus CC, Nedergaard M (1998) Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci USA 95(26):15735–15740

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • D’Antoni S, Berretta A, Bonaccorso CM, Bruno V, Aronica E, Nicoletti F, Catania MV (2008) Metabotropic glutamate receptors in glial cells. Neurochem Res 33(12):2436–2443

    Article  PubMed  Google Scholar 

  • D’Ascenzo M, Fellin T, Terunuma M, Revilla-Sanchez R, Meaney DF, Auberson YP, Moss SJ, Haydon PG (2007) mGluR5 stimulates gliotransmission in the nucleus accumbens. Proc Natl Acad Sci USA 104(6):1995–2000

    Article  PubMed Central  PubMed  Google Scholar 

  • Díaz-Alonso J, Aguado T, de Salas-Quiroga A, Ortega Z, Guzmán M, Galve-Roperh I (2014) CB1 Cannabinoid Receptor-Dependent Activation of mTORC1/Pax6 Signaling Drives Tbr2 Expression and Basal Progenitor Expansion in the Developing Mouse Cortex. Cereb Cortex

  • Duan S, Anderson CM, Keung EC, Chen Y, Chen Y, Swanson RA (2003) P2X7 receptor-mediated release of excitatory amino acids from astrocytes. J Neurosci 23(4):1320–1328

    CAS  PubMed  Google Scholar 

  • Feinberg I, Jones R, Walker JM, Cavness C, March J (1975) Effects of high dosage delta-9-tetrahydrocannabinol on sleep patterns in man. Clin Pharmacol Ther 17(49):458–466

    CAS  PubMed  Google Scholar 

  • Fernández-Ruiz J, Pazos MR, García-Arencibia M, Sagredo O, Ramos JA (2008) Role of CB2 receptors in neuroprotective effects of cannabinoids. Mol Cell Endocrinol 286(1–2)Supplement 1:S91–S96

  • Ferraguti F, Shigemoto R (2006) Metabotropic glutamate receptors. Cell Tissue Res 326(2):483–504

    Article  CAS  PubMed  Google Scholar 

  • Frank MG (2013) Astroglial regulation of sleep homeostasis. Curr Opin Neurobiol 23(5):812–818

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Rill E (1991) The pedunculopontine nucleus. Prog Neurobiol 36:363–389

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Rill E, Charlesworth A, Heister D, Ye M, Hayar A (2008) The developmental decrease in REM sleep: the role of transmitters and electrical coupling. Sleep 31(5):673–690

    PubMed Central  PubMed  Google Scholar 

  • Garcia-Rill E, Simon C, Smith K, Kezunovic N, Hyde J (2011) The pedunculopontine tegmental nucleus: from basic neuroscience to neurosurgical applications. J Neural Transm 118:1397–1407

    Article  PubMed Central  PubMed  Google Scholar 

  • Han J, Kesner P, Metna-Laurent M, Duan T, Xu L, Georges F, Koehl M, Abrous DN, Mendizabal-Zubiaga J, Grandes P, Liu Q, Bai G, Wang W, Xiong L, Ren W, Marsicano G, Zhang X (2012) Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD. Cell 148(5):1039–1050

    Article  CAS  PubMed  Google Scholar 

  • Harata N, Katayama J, Takeshita Y, Murai Y, Akaike N (1996) Two components of metabotropic glutamate responses in acutely dissociated CA3 pyramidal neurons of the rat. Brain Res 711:223–233

    Article  CAS  PubMed  Google Scholar 

  • Hegyi Z, Kis G, Holló K, Ledent C, Antal M (2009) Neuronal and glial localization of the cannabinoid-1 receptor in the superficial spinal dorsal horn of the rodent spinal cord. Eur J Neurosci 30(2):251–262

    Article  PubMed  Google Scholar 

  • Hegyi Z, Holló K, Kis G, Mackie K, Antal M (2012) Differential distribution of diacylglycerol lipase-alpha and N-acylphosphatidylethanolamine-specific phospholipase d immunoreactivity in the superficial spinal dorsal horn of rats. Glia 60(9):1316–1329

    Article  PubMed Central  PubMed  Google Scholar 

  • Hermes ML, Renaud LP (2011) Postsynaptic and presynaptic group II metabotropic glutamate receptor activation reduces neuronal excitability in rat midline paraventricular thalamic nucleus. J Pharmacol Exp Ther 336(3):840–849

    Article  CAS  PubMed  Google Scholar 

  • Herrera-Solís A, Vásquez KG, Prospéro-García O (2010) Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats. Pharmacol Biochem Behav 95:106–112

    Article  PubMed  Google Scholar 

  • Hillard CJ, Manna S, Greenberg MJ, DiCamelli R, Ross RA, Stevenson LA, Murphy V, Pertwee RG, Campbell WB (1999) Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CB1). J Pharmacol Exp Ther 289(3):1427–1433

    CAS  PubMed  Google Scholar 

  • Hubert GW (2004) Smith Y (2004) Age-related changes in the expression of axonal and glial group I metabotropic glutamate receptor in the rat substantia nigra pars reticulata. J Comp Neurol 475(1):95–106

    Article  CAS  PubMed  Google Scholar 

  • Irie T, Fukui I, Ohmori H (2006) Activation of GIRK channels by muscarinic receptors and group II metabotropic glutamate receptors suppresses Golgi cell activity in the cochlear nucleus of mice. J Neurophysiol 96(5):2633–2644

    Article  CAS  PubMed  Google Scholar 

  • Jenkinson N, Nandi D, Muthusamy K, Ray NJ, Gregory R, Stein JF, Aziz TZ (2009) Anatomy, physiology, and pathophysiology of the pedunculopontine nucleus. Mov Disord 24(3):319–328

    Article  PubMed  Google Scholar 

  • Jian K, Cifelli P, Pignatelli A, Frigato E, Belluzzi O (2010) Metabotropic glutamate receptors 1 and 5 differentially regulate bulbar dopaminergic cell function. Brain Res 1354:47–63

    Article  CAS  PubMed  Google Scholar 

  • Kato HK, Kassai H, Watabe AM, Aiba A, Manabe T (2012) Functional coupling of the metabotropic glutamate receptor, InsP3 receptor and L-type Ca2+ channel in mouse CA1 pyramidal cells. J Physiol 590(Pt 13):3019–3034

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Katona I, Freund TF (2012) Multiple functions of endocannabinoid signaling in the brain. Annu Rev Neurosci 35:529–558

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Katona I, Sperlágh B, Sík A, Kőfalvi A, Vizi ES, Mackie K, Freund TF (1999) Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons. J Neurosci 19:4544–4558

    CAS  PubMed  Google Scholar 

  • Kawamura Y, Fukaya M, Maejima T, Yoshida T, Miura E, Watanabe M, Ohno-Shosaku T, Kano M (2006) The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum. J Neurosci 26:2991–3001

    Article  CAS  PubMed  Google Scholar 

  • Knoflach F, Kemp JA (1998) Metabotropic glutamate group II receptors activate a G protein-coupled inwardly rectifying K+ current in neurones of the rat cerebellum. J Physiol 509(Pt 2):347–354

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kohlmeier KA, Christensen MH, Kristensen MP, Kristiansen U (2013) Pharmacological evidence of functional inhibitory metabotrophic glutamate receptors on mouse arousal-related cholinergic laterodorsal tegmental neurons. Neuropharmacology 66:99–113

    Article  CAS  PubMed  Google Scholar 

  • Kőszeghy Á, Vincze J, Rusznák Z, Fu Y, Paxinos G, Csernoch L, Szücs G (2012) Activation of muscarinic receptors increases the activity of the granule neurons of the rat dorsal cochlear nucleus—a calcium imaging study. Pflugers Arch 463(6):829–844

    Article  PubMed  Google Scholar 

  • Libri V, Constanti A, Zibetti M, Postlethwaite M (1997) Metabotropic glutamate receptor subtypes mediating slow inward tail current (IADP) induction and inhibition of synaptic transmission in olfactory cortical neurones. Br J Pharmacol 120(6):1083–1095

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA, Gu H, Ng LL, Palmiter RD, Hawrylycz MJ, Jones AR, Lein ES, Zeng H (2010) A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci 13(1):133–140

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Maloney K, Mainville L, Jones BE (1999) Differential c-Fos expression in cholinergic, monoaminergic, and GABAergic cell groups of the pontomesencephalic tegmentum after paradoxical sleep deprivation and recovery. J Neurosci 19(8):3057–3072

    CAS  PubMed  Google Scholar 

  • Mannaioni G, Marino MJ, Valenti O, Traynelis SF, Conn PJ (2001) Metabotropic glutamate receptors 1 and 5 differentially regulate CA1 pyramidal cell function. J Neurosci 21(16):5925–5934

    CAS  PubMed  Google Scholar 

  • Mena-Segovia J, Sims HM, Magill PJ, Bolam JP (2008) Cholinergic brainstem neurons modulate cortical gamma activity during slow oscillations. J Physiol 586(12):2947–2960

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Min R, Nevian T (2012) Astrocyte signaling controls spike timing-dependent depression at neocortical synapses. Nat Neurosci 15(5):746–753

    Article  CAS  PubMed  Google Scholar 

  • Moldrich G, Wenger T (2000) Localization of the CB1 cannabinoid receptor in the rat brain. An immunohistochemical study. Peptides 21(11):1735–1742

    Article  CAS  PubMed  Google Scholar 

  • Molina-Holgado F, Pinteaux E, Moore JD, Molina-Holgado E, Guaza C, Gibson RM, Rothwell NJ (2003) Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glia. J Neurosci 23(16):6470–6474

    CAS  PubMed  Google Scholar 

  • Murillo-Rodriguez E (2008) The role of the CB1 receptor in the regulation of sleep. Prog Neuropsychopharmacol Biol Psychiatry 32:1420–1427

    Article  CAS  PubMed  Google Scholar 

  • Murillo-Rodriguez E, Millán-Aldaco D, Di Marzo V, Drucker-Colín R (2008) The anandamide membrane transporter inhibitor VDM-11, modulates sleep and c-Fos expression in the rat brain. Neuroscience 157:1–11

    Article  CAS  PubMed  Google Scholar 

  • Murillo-Rodríguez E, Sánchez-Alavez M, Navarro L, Martínez-González D, Drucker-Colín R, Prospéro-García O (1998) Anandamide modulates sleep and memory in rats. Brain Res 812(1–2):270–274

    Article  PubMed  Google Scholar 

  • Murillo-Rodríguez E, Cabeza R, Méndez-Díaz M, Navarro L, Prospéro-García O (2001) Anandamide-induced sleep is blocked by SR141716A, a CB1 receptor antagonist and by U73122, a phospholipase C inhibitor. NeuroReport 12(10):2131–2136

    Article  PubMed  Google Scholar 

  • Navarrete M, Araque A (2008) Endocannabinoids mediate neuron-astrocyte communication. Neuron 58:883–893

    Article  Google Scholar 

  • Navarrete M, Araque A (2010) Endocannabinoids potentiate synaptic transmission through stimulation of astrocytes. Neuron 68:113–126

    Article  CAS  PubMed  Google Scholar 

  • Navarrete M, Perea G, Fernandez de Sevilla D, Gómez-Gonzalo M, Núnez A, Martín ED, Araque A (2012) Astrocytes mediate in vivo cholinergic-induced synaptic plasticity. PLoS Biol 10(2):e1001259

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nett WJ, Oloff SH, McCarthy KD (2002) Hippocampal astrocytes in situ exhibit calcium oscillations that occur independent of neuronal activity. J Neurophysiol 87(1):528–537

    PubMed  Google Scholar 

  • Nimmerjahn A, Kirchhoff F, Kerr JN, Helmchen F (2004) Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo. Nat Methods 1:31–37

    Article  CAS  PubMed  Google Scholar 

  • Niswender CM, Conn PJ (2010) Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 50:295–322

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pace-Schott EF (2009) Sleep architecture. In: Stickgold R, Walker M (eds) The neuroscience of sleep. Elsevier, Amsterdam, pp 10–17

    Google Scholar 

  • Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG (1994) Glutamate-mediated astrocyte-neuron signalling. Nature 369(6483):744–747

    Article  CAS  PubMed  Google Scholar 

  • Parri HR, Gould TM, Crunelli V (2010) Sensory and cortical activation of distinct glial cell subtypes in the somatosensory thalamus of young rats. Eur J Neurosci 32(1):29–40

    Article  PubMed Central  PubMed  Google Scholar 

  • Partridge JG, Lewin AE, Yasko JR, Vicini S (2014) Contrasting actions of Group I metabotropic glutamate receptors in distinct mouse striatal neurones. J Physiol

  • Pasantes Morales H, Schousboe A (1988) Volume regulation in astrocytes: a role for taurine as an osmoeffector. J Neurosci Res 20(4):503–509

    CAS  PubMed  Google Scholar 

  • Paxinos G, Franklin KBJ (2004) The mouse brain atlas in stereotaxic coordinates. Elsevier, USA

    Google Scholar 

  • Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32(8):421–431

    Article  CAS  PubMed  Google Scholar 

  • Petralia RS, Wang YX, Niedzielski AS, Wenthold RJ (1996) The metabotropic glutamate receptors, mGluR2 and mGluR3, show unique postsynaptic, presynaptic and glial localizations. Neuroscience 71(4):949–976

    Article  CAS  PubMed  Google Scholar 

  • Pirttimaki TM, Parri HR (2012) Glutamatergic input–output properties of thalamic astrocytes. Neuroscience 205:18–28

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pirttimaki TM, Hall SD, Parri HR (2011) Sustained neuronal activity generated by glial plasticity. J Neurosci 31(21):7637–7647

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Poisik OV, Mannaioni G, Traynelis S, Smith Y, Conn PJ (2003) Distinct functional roles of the metabotropic glutamate receptors 1 and 5 in the rat globus pallidus. J Neurosci 23(1):122–130

    PubMed  Google Scholar 

  • Rainnie DG, Holmes KH, Shinnick-Gallagher P (1994) Activation of postsynaptic metabotropic glutamate receptors by trans-ACPD hyperpolarizes neurons of the basolateral amygdala. J Neurosci 14:7208–7220

    CAS  PubMed  Google Scholar 

  • Reese NB, Garcia-Rill E, Skinner RD (1995) The pedunculopontine nucleus—auditory input, arousal and pathophysiology. Prog Neurobiol 42:105–133

    Article  Google Scholar 

  • Rodriguez JJ, Mackie K, Pickel VM (2001) Ultrastructural localization of the CB1 cannabinoid receptor in mu-opioid receptor patches of the rat Caudate putamen nucleus. J Neurosci 21(3):823–833

    CAS  PubMed  Google Scholar 

  • Rodriguez-Cueto C, Benito C, Fernández-Ruiz J, Romero J, Hernández-Gálvez M, Gómez-Ruiz M (2013) Changes in Cb1 and Cb2 receptors in the postmortem cerebellum of humans affected by spinocerebellar ataxias. Br J Pharmacol. doi:10.1111/bph.12283

    Google Scholar 

  • Ros H, Magill PJ, Moss J, Bolam JP, Mena-Segovia J (2010) Distinct types of non-cholinergic pedunculopontine neurons are differentially modulated during global brain states. Neuroscience 170:78–91

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rosenberg PA, Knowles R, Knowles KP, Li Y (1994) Beta-adrenergic receptor-mediated regulation of extracellular adenosine in cerebral cortex in culture. J Neurosci 14(5 Pt 2):2953–2965

    CAS  PubMed  Google Scholar 

  • Salio C, Doly S, Fischer J, Franzoni MF, Conrath M (2002) Neuronal and astrocytic localization of the cannabinoid receptor-1 in the dorsal horn of the rat spinal cord. Neurosci Lett 329(1):13–16

    Article  CAS  PubMed  Google Scholar 

  • Schoepp DD (2001) Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system. J Pharmacol Exp Ther 299(1):12–20

    CAS  PubMed  Google Scholar 

  • Schools GP, Kimelberg HK (1999) mGluR3 and mGluR5 are the predominant metabotropic glutamate receptor mRNAs expressed in hippocampal astrocytes acutely isolated from young rats. J Neurosci Res 58(4):533–543

    Article  CAS  PubMed  Google Scholar 

  • Sherman SM (2014) The function of metabotropic glutamate receptors in thalamus and cortex. Neuroscientist 20(2):136–149

    Article  CAS  PubMed  Google Scholar 

  • Shibasaki K, Ikenaka K, Tamalu F, Tominaga M, Ishizaki Y (2014) A novel subtype of astrocytes expressing TRPV4 regulates neuronal excitability via release of gliotransmitters. J Biol Chem

  • Smith RS, Weitz CJ, Araneda RC (2009) Excitatory actions of noradrenaline and metabotropic glutamate receptor activation in granule cells of the accessory olfactory bulb. J Neurophysiol 102(2):1103–1114

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stella N (2004) Cannabinoid signaling in glial cells. Glia 48(4):267–277

    Article  PubMed  Google Scholar 

  • Ster J, Mateos JM, Grewe BF, Coiret G, Corti C, Corsi M, Helmchen F, Gerber U (2011) Enhancement of CA3 hippocampal network activity by activation of group II metabotropic glutamate receptors. Proc Natl Acad Sci USA 108(24):9993–9997

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Steriade M, Datta S, Paré D, Oakson G, Curró Dossi RC (1990) Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems. J Neurosci 10(8):2541–2559

    CAS  PubMed  Google Scholar 

  • Szatkowski M, Barbour B, Attwell D (1990) Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake. Nature 348(6300):443–446

    Article  CAS  PubMed  Google Scholar 

  • Taniguchi H, He M, Wu P, Kim S, Paik R, Sugino K, Kvitsiani D, Fu Y, Lu J, Lin Y, Miyoshi G, Shima Y, Fishell G, Nelson SB, Huang ZJ (2011) A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 71(6):995–1013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tarokh L, Carskadon MA (2009) Sleep in adolescents. In: Stickgold R, Walker M (eds) The neuroscience of sleep. Elsevier, Amsterdam, pp 70–77

    Chapter  Google Scholar 

  • Volterra A, Bezzi P (2002) Release of transmitters from glial cells, chap 13. In: Volterra A et al (eds) The tripartite synapse: glia in synaptic neurotransmission. Oxford University Press, Oxford, pp 164–184

    Google Scholar 

  • Walter L, Stella N (2003) Endothelin-1 increases 2-arachidonoyl glycerol (2-AG) production in astrocytes. Glia 44(1):85–90

    Article  PubMed  Google Scholar 

  • Warr O, Takahashi M, Attwell D (1999) Modulation of extracellular glutamate concentration in rat brain slices by cystine–glutamate exchange. J Physiol 514(Pt 3):783–793

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wilson RI, Nicoll RA (2001) Endogenous cannabinoids mediate retrograde signaling at hippocampal synapses. Nature 410:588–592

    Article  CAS  PubMed  Google Scholar 

  • Wilson-Poe AR, Mitchell VA, Vaughan CW (2013) Postsynaptic mGluR mediated excitation of neurons in midbrain periaqueductal grey. Neuropharmacology 66:348–354

    Article  CAS  PubMed  Google Scholar 

  • Winn P (2006) How best to consider the structure and function of the pedunculopontine tegmental nucleus: evidence from animal studies. J Neurol Sci 248:234–250

    Article  PubMed  Google Scholar 

  • Xi ZX, Baker DA, Shen H, Carson DS, Kalivas PW (2002) Group II metabotropic glutamate receptors modulate extracellular glutamate in the nucleus accumbens. J Pharmacol Exp Ther 300(1):162–171

    Article  CAS  PubMed  Google Scholar 

  • Ye ZC, Wyeth MS, Baltan-Tekkok S, Ransom BR (2003) Functional hemichannels in astrocytes: a novel mechanism of glutamate release. J Neurosci 23(9):3588–3596

    CAS  PubMed  Google Scholar 

  • Zhang Z, Séguéla P (2010) Metabotropic induction of persistent activity in layers II/III of anterior cingulate cortex. Cereb Cortex 20(12):2948–2957

    Article  PubMed  Google Scholar 

  • Zimmer A, Zimmer AM, Hohmann AG, Herkenham M, Bonner TI (1999) Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. Proc Natl Acad Sci USA 96(10):5780–5785

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zur Nieden R, Deitmer JW (2006) The role of metabotropic glutamate receptors for the generation of calcium oscillations in rat hippocampal astrocytes in situ. Cereb Cortex 16(5):676–687

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by TÁMOP-4.2.2/B-10/1-2010-0024 and TÁMOP-4.2.2/A-11/1-KONV-2012-0025, the LP 003/2011 (TB), the Hungarian Academy of Sciences (grant number: MTA-TKI 242; AM) the János Bolyai Research Scholarship of the Hungarian Academy of Sciences, the Hungarian National Brain Research Program (KTIA_13_NAP-A-I/10. to BP and KTIA_13_NAP-A-I/8. to AM; KTIA_NAP_13-2-2014-0005 to PS), the research support grant of the Gedeon Richter Centenary Foundation, and the ‘Ányos Jedlik Scholarship’ of the ‘National Excellence Program’ of Hungary and the European Union TÁMOP 4.2.4. A/2-11-1-2012-0001 (ÁK). The authors are indebted to Professor Andreas Zimmer for providing us the CB1 knockout mouse strain, and to Professor Géza Szücs, Professor László Csernoch, Dr. Zoltán Rusznák, Dr. Attila Oláh and Dr. Attila Szöllősi for their help and valuable suggestions, and to Mrs. A. Varga for her technical support.

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, 4012, Debrecen, Hungary

    Áron Kőszeghy, Adrienn Kovács, Tamás Bíró, Péter Szücs, János Vincze & Balázs Pál

  2. “DE-MTA Lendület” Cellular Physiology Research Group of the Hungarian Academy of Sciences, Debrecen, Hungary

    Tamás Bíró

  3. Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Zoltán Hegyi & Miklós Antal

  4. MTA-DE Neuroscience Research Group, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Miklós Antal

  5. MTA-DE-NAP B-Pain Control Research Group, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Péter Szücs

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  1. Áron Kőszeghy
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  2. Adrienn Kovács
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  3. Tamás Bíró
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  4. Péter Szücs
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  5. János Vincze
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  6. Zoltán Hegyi
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  8. Balázs Pál
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Correspondence to Balázs Pál.

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Á. Kőszeghy and A. Kovács contributed equally to this work.

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Kőszeghy, Á., Kovács, A., Bíró, T. et al. Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes. Brain Struct Funct 220, 3023–3041 (2015). https://doi.org/10.1007/s00429-014-0842-5

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