Brain Structure and Function

, Volume 222, Issue 1, pp 247–266 | Cite as

Direct presynaptic and indirect astrocyte-mediated mechanisms both contribute to endocannabinoid signaling in the pedunculopontine nucleus of mice

  • A. Kovács
  • Cs. Bordás
  • T. Bíró
  • Z. Hegyi
  • M. Antal
  • P. Szücs
  • Balázs PálEmail author
Original Article


The pedunculopontine nucleus (PPN), a cholinergic nucleus of the reticular activating system, is known to be involved in the regulation of sleep and wakefulness. Endogenous and exogenous cannabinoids, by systemic or local administration to the pedunculopontine nucleus, can both influence sleep. We previously demonstrated that activation of astrocytes by cannabinoid type 1 (CB1) receptor agonists was able to modulate the membrane potential of PPN neurons, even in the presence of blockers of fast synaptic neurotransmission. In the present work, we provide evidence that synaptic inputs of PPN neurons are also affected by activation of presynaptic and astrocytic CB1 receptors. Using slice electrophysiology combined with calcium imaging, optogenetics and immunohistochemistry, we revealed a direct presynaptic inhibitory action on inhibitory postsynaptic currents, along with a mild increase of excitatory postsynaptic currents during CB1 receptor stimulation. Besides inhibition of excitatory and inhibitory neurotransmission through stimulation of presynaptic CB1 receptors, astrocyte- and mGluR-dependent tonic inhibition and excitation also developed. The mild stimulatory action of CB1 receptor activation on excitatory neurotransmission is the combination of astrocyte-dependent tonic excitation on excitatory neurons and the canonical presynaptic CB1 receptor activation and consequential inhibition of excitatory synaptic neurotransmission, whereas the astrocyte-dependent stimulatory action was not observed in inhibitory neurotransmission within the PPN. Our findings demonstrate that endocannabinoids act in the PPN via a dual pathway, consisting of a direct presynaptic and an indirect, astrocyte-mediated component, regulating synaptic strength and neuronal activity via independent mechanisms.


Pedunculopontine nucleus CB1 receptor Optogenetics Astrocyte Neuromodulation 



This work was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences, the Szodoray Fellowship of the University of Debrecen, the Hungarian National Brain Research Program (KTIA_13_NAP-A-I/10 to BP; KTIA_NAP_13-1-2013-0001 to MA; KTIA_NAP_13-2-2014-0005 to PS) and the Hungarian Academy of Sciences (MTA-TKI 242; MA), and TÁMOP-4.2.2.B-15/1/KONV-2015-0001 (AK, CB). The authors are indebted to Professor Andreas Zimmer for providing us the CB1 knockout mouse strain and to Professor László Csernoch and Dr. Péter Szentesi for providing Rhod-2 fluorescent dye and for the valuable discussion of the results of this project.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interest.

Supplementary material

429_2016_1214_MOESM1_ESM.docx (139 kb)
Supplementary material 1 (DOCX 139 kb)


  1. Angulo MC, Kozlov AS, Charpak S, Audinat E (2004) Glutamate released from glial cells synchronizes neuronal activity in the hippocampus. J Neurosci 24(31):6920–6927CrossRefPubMedGoogle Scholar
  2. Belluzzi O, Puopolo M, Benedusi M, Kratskin I (2004) Selective neuroinhibitory effects of taurine in slices of rat main olfactory bulb. Neuroscience 124(4):929–944CrossRefPubMedGoogle Scholar
  3. Beppu K, Sasaki T, Tanaka KF, Yamanaka A, Fukazawa Y, Shigemoto R, Matsui K (2014) Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. Neuron 81(2):314–320CrossRefPubMedGoogle Scholar
  4. Castillo PE, Younts TJ, Chávez AE, Hashimotodani Y (2012) Endocannabinoid signaling and synaptic function. Neuron 76(1):70–81CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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):7067–7076PubMedGoogle Scholar
  6. Chavis P, Fagni L, Bockaert J, Lansman JB (1995) Modulation of calcium channels by metabotropic glutamate receptors in cerebellar granule cells. Neuropharmacology 34(8):929–937CrossRefPubMedGoogle Scholar
  7. Chen N, Sugihara H, Sharma J, Perea G, Petravicz J, Le C, Sur M (2012) Nucleus basalis-enabled stimulus-specific plasticity in the visual cortex is mediated by astrocytes. PNAS 109(41):E2832–E2841CrossRefPubMedPubMedCentralGoogle Scholar
  8. Chen J, Tan Z, Zeng L, Zhang X, He Y, Gao W, Wu X, Li Y, Bu B, Wang W, Duan S (2013) Heterosynaptic long-term depression mediated by ATP released from astrocytes. Glia 61(2):178–191CrossRefPubMedGoogle Scholar
  9. 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):e37320CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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):15735–15740CrossRefPubMedPubMedCentralGoogle Scholar
  11. D’Ascenso M, Fellin T, Terunuma M, Revilla-Sancez R, Meaney DF, Aubertson YP, Moss SJ, Haydon PG (2007) mGluR5 stimulates gliotransmission in the nucleus accumbens. PNAS 104(6):1995–2000CrossRefGoogle Scholar
  12. Deisseroth K, Feng G, Majewska AK, Miesenböck G, Ting A, Schnitzer MJ (2006) Next-generation optical technologies for illuminating genetically targeted brain circuits. J Neurosci 26(41):10380–10386CrossRefPubMedPubMedCentralGoogle Scholar
  13. Diana MA, Marty A (2004) Endocannabinoid-mediated short-term synaptic plasticity: depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE). Br J Pharmacol 142(1):9–19CrossRefPubMedPubMedCentralGoogle Scholar
  14. Diana MA, Levenes C, Mackie K, Marty A (2002) Short-term retrograde inhibition of GABAergic synaptic currents in rat Purkinje cells is mediated by endogenous cannabinoids. J Neurosci 22(1):200–208PubMedGoogle Scholar
  15. 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):1320–1328PubMedGoogle Scholar
  16. 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):458–466CrossRefPubMedGoogle Scholar
  17. Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG, Carmignoto G (2004) Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43:729–743CrossRefPubMedGoogle Scholar
  18. Fenno L, Yizhar O, Deisseroth K (2011) The development and application of optogenetics. Annu Rev Neurosci 34:389–412CrossRefPubMedGoogle Scholar
  19. Figueiredo M, Lane S, Tang F, Liu BH, Hewinson J, Marina N, Kasymov V, Souslova EA, Chudakov DM, Gourine AV, Teschemacher AG, Kasparov S (2011) Optogenetic experimentation on astrocytes. Exp Physiol 96(1):40–50CrossRefPubMedGoogle Scholar
  20. Figueiredo M, Lane S, Stout RF Jr, Liu B, Parpura V, Teschemacher AG, Kasparov S (2014) Comparative analysis of optogenetic actuators in cultured astrocytes. Cell Calcium 56(3):208–214CrossRefPubMedPubMedCentralGoogle Scholar
  21. Garcia-Rill E (1991) The pedunculopontine nucleus. Prog Neurobiol 36:363–389CrossRefPubMedGoogle Scholar
  22. 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 118:1397–1407CrossRefPubMedGoogle Scholar
  23. Garcia-Rill E, Kezunovic N, Hyde J, Simon C, Beck P, Urbano FJ (2013) Coherence and frequency in the reticular activating system (RAS). Sleep Med Rev 17(3):227–238CrossRefPubMedGoogle Scholar
  24. Gourine AV, Kasymov V, Marina N, Tang F, Figueiredo MF, Lane S, Teschemacher AG, Spyer KM, Deisseroth K, Kasparov S (2010) Astrocytes control breathing through pH-dependent release of ATP. Science 329(5991):571–575CrossRefPubMedPubMedCentralGoogle Scholar
  25. Guan X, Cravatt BF, Ehring GR, Hall JE, Boger DL, Lerner RA, Gilula NB (1997) The sleep-inducing lipid oleamide deconvolutes gap junction communication and calcium wave transmission in glial cells. J Cell Biol 139(7):1785–1792CrossRefPubMedPubMedCentralGoogle Scholar
  26. 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):1039–1050CrossRefPubMedGoogle Scholar
  27. 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):251–262CrossRefPubMedGoogle Scholar
  28. 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):840–849CrossRefPubMedGoogle Scholar
  29. 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 95:106–112CrossRefPubMedGoogle Scholar
  30. Hoffman AF, Lupica CR (2000) Mechanisms of cannabinoid inhibition of GABA(A) synaptic transmission in the hippocampus. J Neurosci 20(7):2470–2479PubMedGoogle Scholar
  31. 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):2633–2644CrossRefPubMedGoogle Scholar
  32. Jabaudon D, Shimamoto K, Yasuda-Kamatani Y, Scanziani M, Gahwiler BH, Gerber U (1999) Inhibition of uptake unmasks rapid extracellular turnover of glutamate of nonvesicular origin. PNAS 96:8733–8738CrossRefPubMedPubMedCentralGoogle Scholar
  33. Ji ZG, Wang H (2015) Optogenetic control of astrocytes: is it possible to treat astrocyte-related epilepsy? Brain Res Bull 110:20–25CrossRefPubMedGoogle Scholar
  34. 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 1354:47–63CrossRefPubMedGoogle Scholar
  35. Kano M (2014) Control of synaptic function by endocannabinoid-mediated retrograde signaling. Proc Jpn Acad Ser B 90:235–250CrossRefGoogle Scholar
  36. 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):3019–3034CrossRefPubMedPubMedCentralGoogle Scholar
  37. Katona I, Freund TF (2012) Multiple functions of endocannabinoid signaling in the brain. Annu Rev Neurosci 35:529–558CrossRefPubMedPubMedCentralGoogle Scholar
  38. 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 19:4544–4558PubMedGoogle Scholar
  39. Katona I, Urban GM, Wallace M, Ledent C, Jung KM, Piomelli D, Mackie K, Freund TF (2006) Molecular composition of the endocannabinoid system at glutamatergic synapses. J Neurosci 26:5628–5637CrossRefPubMedPubMedCentralGoogle Scholar
  40. 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 66:99–113CrossRefPubMedGoogle Scholar
  41. 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):829–844CrossRefPubMedGoogle Scholar
  42. Kőszeghy A, Kovács A, Bíró T, Szücs P, Vincze J, Hegyi Z, Antal M, Pál B (2015) Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes. Brain Struct Funct 220(5):3023–3041CrossRefPubMedGoogle Scholar
  43. Kovács A, Bordás C, Pál B (2015) Cholinergic and endocannabinoid neuromodulatory effects overlap on neurons of the pedunculopontine nucleus of mice. Neuroreport 26(5):273–278CrossRefPubMedGoogle Scholar
  44. Kozlov AS, Angulo MC, Audinat E, Charpak S (2006) Target cell-specific modulation of neuronal activity by astrocytes. PNAS 103(26):10058–10063CrossRefPubMedPubMedCentralGoogle Scholar
  45. Kreitzer AC, Regehr WG (2001) Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron 29(3):717–727CrossRefPubMedGoogle Scholar
  46. Le Meur K, Galante M, Angulo MC, Audinat E (2007) Tonic activation of NMDA receptors by ambient glutamate of non-synaptic origin in the rat hippocampus. J Physiol 580(Pt. 2):373–383CrossRefPubMedGoogle Scholar
  47. Lee S, Yoon BE, Berglund K, Oh SJ, Park H, Shin HS, Augustine GJ, Lee CJ (2010) Channel-mediated tonic GABA release from glia. Science 330(6005):790–796CrossRefPubMedGoogle Scholar
  48. 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):1083–1095CrossRefPubMedPubMedCentralGoogle Scholar
  49. Llano I, Leresche N, Marty A (1991) Calcium entry increases the sensitivity of cerebellar Purkinje cells to applied GABA and decreases inhibitory synaptic currents. Neuron 6:565–574CrossRefPubMedGoogle Scholar
  50. Lovinger DM (2008) Presynaptic modulation by endocannabinoids. Handb Exp Pharmacol 184:435–477CrossRefGoogle Scholar
  51. Moldrich G, Wenger T (2000) Localization of the CB1 cannabinoid receptor in the rat brain. An immunohistochemical study. Peptides 21(11):1735–1742CrossRefPubMedGoogle Scholar
  52. Murillo-Rodriguez E (2008) The role of the CB1 receptor in the regulation of sleep. Prog Neuropsychopharmacol Biol Psychiatry 32:1420–1427CrossRefPubMedGoogle Scholar
  53. 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 157:1–11CrossRefPubMedGoogle Scholar
  54. Navarrete M, Araque A (2008) Endocannabinoids mediate neuron-astrocyte communication. Neuron 58:883–893CrossRefGoogle Scholar
  55. Navarrete M, Araque A (2010) Endocannabinoids potentiate synaptic transmission through stimulation of astrocytes. Neuron 68:113–126CrossRefPubMedGoogle Scholar
  56. Navarrete M, Perea G, Fernandez de Sevilla D, Gómez-Gonzalo M, Núñez A, Martín ED, Araque A (2012) Astrocytes mediate in vivo cholinergic-induced synaptic plasticity. PLoS Biol 10(2):e1001259CrossRefPubMedPubMedCentralGoogle Scholar
  57. Nimmerjahn A, Kirchhoff F, Kerr JN, Helmchen F (2004) Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo. Nat Methods 1:31–37CrossRefPubMedGoogle Scholar
  58. Ohno-Shosaku T, Tsubokawa H, Mizushima I, Yoneda N, Zimmer A, Kano M (2002) Presynaptic cannabinoid sensitivity is a major determinant of depolarization-induced retrograde suppression at hippocampal synapses. J Neurosci 22(10):3864–3872PubMedGoogle Scholar
  59. Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG (1994) Glutamate-mediated astrocyte-neuron signalling. Nature 369:744–747CrossRefPubMedGoogle Scholar
  60. Partridge JG, Lewin AE, Yasko JR, Vicini S (2014) Contrasting actions of Group I metabotropic glutamate receptors in distinct mouse striatal neurones. J Physiol 592(Pt 13):2721–2733CrossRefPubMedPubMedCentralGoogle Scholar
  61. Pasantes Morales H, Schousboe A (1988) Volume regulation in astrocytes: a role for taurine as an osmoeffector. J Neurosci Res 20(4):503–509PubMedGoogle Scholar
  62. Perea G, Yang A, Boyden ES, Sur M (2014) Optogenetic astrocyte activation modulates response selectivity of visual cortex neurons in vivo. Nat Commun 5:3262CrossRefPubMedPubMedCentralGoogle Scholar
  63. Petzold A, Valencia M, Pál B, Mena-Segovia J (2015) Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms. Front Neural Circuits 9:68CrossRefPubMedPubMedCentralGoogle Scholar
  64. 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 14:7208–7220PubMedGoogle Scholar
  65. Rasooli-Nejad S, Palygin O, Lalo U, Pankratov Y (2014) Cannabinoid receptors contribute to astroglial Ca2+-signalling and control of synaptic plasticity in the neocortex. Philos Trans R Soc Lond B Biol Sci 69(1654):20140077CrossRefGoogle Scholar
  66. Reese NB, Garcia-Rill E, Skinner RD (1995) The pedunculopontine nucleus—auditory input, arousal and pathophysiology. Prog Neurobiol 42:105–133CrossRefGoogle Scholar
  67. 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):823–833PubMedGoogle Scholar
  68. 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 170:78–91CrossRefPubMedPubMedCentralGoogle Scholar
  69. 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):2953–2965PubMedGoogle Scholar
  70. 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):13–16CrossRefPubMedGoogle Scholar
  71. Sasaki T, Beppu K, Tanaka KF, Fukazawa Y, Shigemoto R, Matsui K (2012) Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation. Proc Natl Acad Sci USA 109(50):20720–20725CrossRefPubMedPubMedCentralGoogle Scholar
  72. 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):1103–1114CrossRefPubMedPubMedCentralGoogle Scholar
  73. Soni N, Kohlmeier KA (2015) Endocannabinoid CB1 receptor-mediated rises in Ca2+ and depolarization-induced suppression of inhibition within the laterodorsal tegmental nucleus. Brain Struct FunctGoogle Scholar
  74. Soni N, Satpathy S, Kohlmeier KA (2014) Neurophysiological evidence for the presence of cannabinoid CB1 receptors in the laterodorsal tegmental nucleus. Eur J Neurosci 40(11):3635–3652CrossRefPubMedGoogle Scholar
  75. 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):9993–9997CrossRefPubMedPubMedCentralGoogle Scholar
  76. Szatkowski M, Barbour B, Attwell D (1990) Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake. Nature 348(6300):443–446CrossRefPubMedGoogle Scholar
  77. Trettel J, Levine ES (2003) Endocannabinoids mediate rapid retrograde signaling at interneuron → pyramidal neuron synapses of the neocortex. J Neurophysiol 89:2334–2338CrossRefPubMedGoogle Scholar
  78. Urbano FJ, Kezunovic N, Hyde J, Simon C, Beck P, Garcia-Rill E (2012) Gamma band activity in the reticular activating system. Front Neurol 3:6CrossRefPubMedPubMedCentralGoogle Scholar
  79. Vincent P, Armstrong CM, Marty A (1992) Inhibitory synaptic currents in rat cerebellar Purkinje cells: modulation by postsynaptic depolarization. J Physiol 456:453–471CrossRefPubMedPubMedCentralGoogle Scholar
  80. 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):783–793CrossRefPubMedPubMedCentralGoogle Scholar
  81. Yanovsky Y, Mades S, Misgeld U (2003) Retrograde signaling changes the venue of postsynaptic inhibition in rat substantia nigra. Neuroscience 122(2):317–328CrossRefPubMedGoogle Scholar
  82. Ye ZC, Wyeth MS, Baltan-Tekkok S, Ransom BR (2003) Functional hemichannels in astrocytes: a novel mechanism of glutamate release. J Neurosci 23(9):3588–3596PubMedGoogle Scholar
  83. Ye M, Hayar A, Strotman B, Garcia-Rill E (2010) Cholinergic modulation of fast inhibitory and excitatory transmission to pedunculopontine thalamic projecting neurons. J Neurophysiol 103(5):2417–2432CrossRefPubMedPubMedCentralGoogle Scholar
  84. Zhang F, Wang LP, Boyden ES, Deisseroth K (2006) Channelrhodopsin-2 and optical control of excitable cells. Nat Methods 3(10):785–792CrossRefPubMedGoogle Scholar
  85. 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):5780–5785CrossRefPubMedPubMedCentralGoogle Scholar
  86. Zucker RS, Regehr WG (2002) Short-term synaptic plasticity. Annu Rev Physiol 64:355–405CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • A. Kovács
    • 1
  • Cs. Bordás
    • 1
  • T. Bíró
    • 1
    • 2
  • Z. Hegyi
    • 3
  • M. Antal
    • 3
    • 4
  • P. Szücs
    • 1
    • 5
  • Balázs Pál
    • 1
    Email author
  1. 1.Department of Physiology, Faculty of MedicineUniversity of DebrecenDebrecenHungary
  2. 2.Department of Immunology, Faculty of MedicineUniversity of DebrecenDebrecenHungary
  3. 3.Department of Anatomy, Histology and Embryology, Faculty of MedicineUniversity of DebrecenDebrecenHungary
  4. 4.MTA-DE Neuroscience Research GroupDebrecenHungary
  5. 5.MTA-DE-NAP B-Pain Control Research GroupDebrecenHungary

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