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Endocannabinoid CB1 receptor-mediated rises in Ca2+ and depolarization-induced suppression of inhibition within the laterodorsal tegmental nucleus

Abstract

Cannabinoid type 1 receptors (CB1Rs) are functionally active within the laterodorsal tegmental nucleus (LDT), which is critically involved in control of rapid eye movement sleep, cortical arousal, and motivated states. To further characterize the cellular consequences of activation of CB1Rs in this nucleus, we examined whether CB1R activation led to rises in intracellular Ca2+ ([Ca2+]i) and whether processes shown in other regions to involve endocannabinoid (eCB) transmission were present in the LDT. Using a combination of Ca2+ imaging in multiple cells loaded with Ca2+ imaging dye via ‘bulk-loading’ or in single cells loaded with dye via a patch-clamp electrode, we found that WIN 55212-2 (WIN-2), a potent CB1R agonist, induced increases in [Ca2+]i which were sensitive to AM251, a CB1R antagonist. A proportion of rises persisted in TTX and/or low-extracellular Ca2+ conditions. Attenuation of these increases by a reversible inhibitor of sarcoplasmic reticulum Ca2+-ATPases, suggests these rises occurred following release of Ca2+ from intracellular stores. Under voltage clamp conditions, brief, direct depolarization of LDT neurons resulted in a decrease in the frequency and amplitude of AM251-sensitive, inhibitory postsynaptic currents (IPSCs), which was an action sensitive to presence of a Ca2+ chelator. Finally, actions of DHPG, a mGlu1R agonist, on IPSC activity were examined and found to result in an AM251- and BAPTA-sensitive inhibition of both the frequency and amplitude of sIPSCs. Taken together, our data further characterize CB1R and eCB actions in the LDT and indicate that eCB transmission could play a role in the processes governed by this nucleus.

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References

  1. Alger BE, Kim J (2011) Supply and demand for endocannabinoids. Trends Neurosci 34:304–315

  2. Allen Mouse Brain Atlas [Internet] (2012) Allen Institute for Brain Science. http://mouse.brain-map.org/. Accessed 7 July 2014

  3. Berrendero F, Garcia-Gil L, Hernandez ML, Romero J, Cebeira M, de Miguel R, Ramos JA, Fernandez-Ruiz JJ (1998) Localization of mRNA expression and activation of signal transduction mechanisms for cannabinoid receptor in rat brain during fetal development. Development 125:3179–3188

  4. Berrendero F, Sepe N, Ramos JA, Di Marzo V, Fernandez-Ruiz JJ (1999) Analysis of cannabinoid receptor binding and mRNA expression and endogenous cannabinoid contents in the developing rat brain during late gestation and early postnatal period. Synapse 33:181–191

  5. Boucetta S, Jones BE (2009) Activity profiles of cholinergic and intermingled GABAergic and putative glutamatergic neurons in the pontomesencephalic tegmentum of urethane-anesthetized rats. J Neurosci 29:4664–4674

  6. Boucetta S, Cisse Y, Mainville L, Morales M, Jones BE (2014) Discharge profiles across the sleep-waking cycle of identified cholinergic, GABAergic, and glutamatergic neurons in the pontomesencephalic tegmentum of the rat. J Neurosci 34:4708–4727

  7. Brenowitz SD, Regehr WG (2003) Calcium dependence of retrograde inhibition by endocannabinoids at synapses onto Purkinje cells. J Neurosci 23:6373–6384

  8. Brown SP, Safo PK, Regehr WG (2004) Endocannabinoids inhibit transmission at granule cell to Purkinje cell synapses by modulating three types of presynaptic calcium channels. J Neurosci 24:5623–5631

  9. Burkey TH, Quock RM, Consroe P, Ehlert FJ, Hosohata Y, Roeske WR, Yamamura HI (1997) Relative efficacies of cannabinoid CB1 receptor agonists in the mouse brain. Eur J Pharmacol 336:295–298

  10. Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (2005) International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev 57:411–425

  11. Caulfield MP, Brown DA (1992) Cannabinoid receptor agonists inhibit Ca current in NG108-15 neuroblastoma cells via a pertussis toxin-sensitive mechanism. Br J Pharmacol 106:231–232

  12. Chevaleyre V, Castillo PE (2003) Heterosynaptic LTD of hippocampal GABAergic synapses: a novel role of endocannabinoids in regulating excitability. Neuron 38:461–472

  13. Christensen MH, Ishibashi M, Nielsen ML, Leonard CS, Kohlmeier KA (2014) Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: Implications for the heightened adolescent susceptibility to nicotine addiction. Neuropharmacology 85:263–283

  14. Compton DR, Gold LH, Ward SJ, Balster RL, Martin BR (1992) Aminoalkylindole analogs: cannabimimetic activity of a class of compounds structurally distinct from delta 9-tetrahydrocannabinol. J Pharmacol Exp Ther 263:1118–1126

  15. Dautan D, Huerta-Ocampo I, Witten IB, Deisseroth K, Bolam JP, Gerdjikov T, Mena-Segovia J (2014) A major external source of cholinergic innervation of the striatum and nucleus accumbens originates in the brainstem. J Neurosci 34:4509–4518

  16. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–1949

  17. 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 22:200–208

  18. Drevets WC, Gautier C, Price JC, Kupfer DJ, Kinahan PE, Grace AA, Price JL, Mathis CA (2001) Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria. Biol Psychiatry 49:81–96

  19. Edwards DA, Kim J, Alger BE (2006) Multiple mechanisms of endocannabinoid response initiation in hippocampus. J Neurophysiol 95:67–75

  20. el Mansari M, Sakai K, Jouvet M (1989) Unitary characteristics of presumptive cholinergic tegmental neurons during the sleep-waking cycle in freely moving cats. Exp Brain Res 76:519–529

  21. Endoh T (2006) Pharmacological characterization of inhibitory effects of postsynaptic opioid and cannabinoid receptors on calcium currents in neonatal rat nucleus tractus solitarius. Br J Pharmacol 147:391–401

  22. 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 17:458–466

  23. Feinberg I, Jones R, Walker J, Cavness C, Floyd T (1976) Effects of marijuana extract and tetrahydrocannabinol on electroencephalographic sleep patterns. Clin Pharmacol Ther 19:782–794

  24. Fergusson DM, Horwood LJ (2000) Does cannabis use encourage other forms of illicit drug use? Addiction 95:505–520

  25. Fernandez-Ruiz JJ, Berrendero F, Hernandez ML, Romero J, Ramos JA (1999) Role of endocannabinoids in brain development. Life Sci 65:725–736

  26. Forster GL, Blaha CD (2000) Laterodorsal tegmental stimulation elicits dopamine efflux in the rat nucleus accumbens by activation of acetylcholine and glutamate receptors in the ventral tegmental area. Eur J Neurosci 12:3596–3604

  27. Freund TF, Katona I, Piomelli D (2003) Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83:1017–1066

  28. Gaoni Y, Mechoulam R (1964) Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 86:1646

  29. Gatley SJ, Gifford AN, Volkow ND, Lan R, Makriyannis A (1996) 123I-labeled AM251: a radioiodinated ligand which binds in vivo to mouse brain cannabinoid CB1 receptors. Eur J Pharmacol 307:331–338

  30. Gatley SJ, Lan R, Pyatt B, Gifford AN, Volkow ND, Makriyannis A (1997) Binding of the non-classical cannabinoid CP 55,940, and the diarylpyrazole AM251 to rodent brain cannabinoid receptors. Life Sci 61:PL191–PL197

  31. Giordano TP, Tropea TF, Satpute SS, Sinnegger-Brauns MJ, Striessnig J, Kosofsky BE, Rajadhyaksha AM (2010) Molecular switch from L-type Ca v 1.3 to Ca v 1.2 Ca2+ channel signaling underlies long-term psychostimulant-induced behavioral and molecular plasticity. J Neurosci 30:17051–17062

  32. Glass M, Felder CC (1997) Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor. J Neurosci 17:5327–5333

  33. Glitsch M, Llano I, Marty A (1996) Glutamate as a candidate retrograde messenger at interneurone-Purkinje cell synapses of rat cerebellum. J Physiol 497(Pt 2):531–537

  34. Guzman JN, Sanchez-Padilla J, Wokosin D, Kondapalli J, Ilijic E, Schumacker PT, Surmeier DJ (2010) Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature 468:696–700

  35. Heifets BD, Castillo PE (2009) Endocannabinoid signaling and long-term synaptic plasticity. Annu Rev Physiol 71:283–306

  36. Hell JW, Westenbroek RE, Warner C, Ahlijanian MK, Prystay W, Gilbert MM, Snutch TP, Catterall WA (1993) Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits. J Cell Biol 123:949–962

  37. Hentges ST, Low MJ, Williams JT (2005) Differential regulation of synaptic inputs by constitutively released endocannabinoids and exogenous cannabinoids. J Neurosci 25:9746–9751

  38. Honda T, Semba K (1995) An ultrastructural study of cholinergic and non-cholinergic neurons in the laterodorsal and pedunculopontine tegmental nuclei in the rat. Neuroscience 68:837–853

  39. Hope BT, Michael GJ, Knigge KM, Vincent SR (1991) Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci USA 88:2811–2814

  40. Howlett AC (2005) Cannabinoid receptor signaling. Handb Exp Pharmacol 168:53–79

  41. Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161–202

  42. Howlett AC, Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, Porrino LJ (2004) Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology 47(Suppl 1):345–358

  43. Huang YY, Malenka RC (1993) Examination of TEA-induced synaptic enhancement in area CA1 of the hippocampus: the role of voltage-dependent Ca2+ channels in the induction of LTP. J Neurosci 13:568–576

  44. Ishibashi M, Leonard CS, Kohlmeier KA (2009) Nicotinic activation of laterodorsal tegmental neurons: implications for addiction to nicotine. Neuropsychopharmacology 34:2529–2547

  45. Ishibashi M, Gumenchuk I, Leonard CS (2010) L-type calcium channels containing CaV 1.3 contribute to voltage-dependent calcuim influx in mouse laterodorsal tegmental neurons. Soc Neurosci (Abstract) 35

  46. Isokawa M, Alger BE (2005) Retrograde endocannabinoid regulation of GABAergic inhibition in the rat dentate gyrus granule cell. J Physiol 567:1001–1010

  47. Isokawa M, Alger BE (2006) Ryanodine receptor regulates endogenous cannabinoid mobilization in the hippocampus. J Neurophysiol 95:3001–3011

  48. Isope P, Murphy TH (2005) Low threshold calcium currents in rat cerebellar Purkinje cell dendritic spines are mediated by T-type calcium channels. J Physiol 562:257–269

  49. Iversen L (2003) Cannabis and the brain. Brain 126:1252–1270

  50. Jia HG, Yamuy J, Sampogna S, Morales FR, Chase MH (2003) Colocalization of gamma-aminobutyric acid and acetylcholine in neurons in the laterodorsal and pedunculopontine tegmental nuclei in the cat: a light and electron microscopic study. Brain Res 992:205–219

  51. Jones BE, Webster HH (1988) Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. I. Effects upon the cholinergic innervation of the brain. Brain Res 451:13–32

  52. Jones BE, Yang TZ (1985) The efferent projections from the reticular formation and the locus coeruleus studied by anterograde and retrograde axonal transport in the rat. J Comp Neurol 242:56–92

  53. Kayama Y, Ohta M, Jodo E (1992) Firing of ‘possibly’ cholinergic neurons in the rat laterodorsal tegmental nucleus during sleep and wakefulness. Brain Res 569:210–220

  54. Kim J, Isokawa M, Ledent C, Alger BE (2002) Activation of muscarinic acetylcholine receptors enhances the release of endogenous cannabinoids in the hippocampus. J Neurosci 22:10182–10191

  55. Kohlmeier KA, Leonard CS (2006) Transmitter modulation of spike-evoked calcium transients in arousal related neurons: muscarinic inhibition of SNX-482-sensitive calcium influx. Eur J Neurosci 23:1151–1162

  56. Kohlmeier KA, Inoue T, Leonard CS (2004) Hypocretin/orexin peptide signaling in the ascending arousal system: elevation of intracellular calcium in the mouse dorsal raphe and laterodorsal tegmentum. J Neurophysiol 92:221–235

  57. Kohlmeier KA, Soja PJ, Kristensen MP (2006) Disparate cholinergic currents in rat principal trigeminal sensory nucleus neurons mediated by M1 and M2 receptors: a possible mechanism for selective gating of afferent sensory neurotransmission. Eur J Neurosci 23:3245–3258

  58. Kohlmeier KA, Watanabe S, Tyler CJ, Burlet S, Leonard CS (2008) Dual orexin actions on dorsal raphe and laterodorsal tegmentum neurons: noisy cation current activation and selective enhancement of Ca2+ transients mediated by L-type calcium channels. J Neurophysiol 100:2265–2281

  59. Kohlmeier KA, Ishibashi M, Wess J, Bickford ME, Leonard CS (2012) Knockouts reveal overlapping functions of M(2) and M(4) muscarinic receptors and evidence for a local glutamatergic circuit within the laterodorsal tegmental nucleus. J Neurophysiol 108:2751–2766

  60. 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

  61. Kondo S, Kondo H, Nakane S, Kodaka T, Tokumura A, Waku K, Sugiura T (1998) 2-Arachidonoylglycerol, an endogenous cannabinoid receptor agonist: identification as one of the major species of monoacylglycerols in various rat tissues, and evidence for its generation through Ca2+ -dependent and -independent mechanisms. FEBS Lett 429:152–156

  62. Koszeghy A, Kovacs A, Biro T, Szucs P, Vincze J, Hegyi Z, Antal M, Pal B (2014) Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes. Brain Struct Funct. doi:10.1007/s00429-014-0842-5

  63. Kreitzer AC, Regehr WG (2001) Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron 29:717–727

  64. Kullmann DM, Perkel DJ, Manabe T, Nicoll RA (1992) Ca2+ entry via postsynaptic voltage-sensitive Ca2+ channels can transiently potentiate excitatory synaptic transmission in the hippocampus. Neuron 9:1175–1183

  65. Lammel S, Lim BK, Ran C, Huang KW, Betley MJ, Tye KM, Deisseroth K, Malenka RC (2012) Input-specific control of reward and aversion in the ventral tegmental area. Nature 491:212–217

  66. Lauckner JE, Hille B, Mackie K (2005) The cannabinoid agonist WIN55,212-2 increases intracellular calcium via CB1 receptor coupling to Gq/11 G proteins. Proc Natl Acad Sci USA 102:19144–19149

  67. Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci USA 105:2699–2704

  68. Lenz RA, Alger BE (1999) Calcium dependence of depolarization-induced suppression of inhibition in rat hippocampal CA1 pyramidal neurons. J Physiol 521(Pt 1):147–157

  69. Lenz RA, Wagner JJ, Alger BE (1998) N- and L-type calcium channel involvement in depolarization-induced suppression of inhibition in rat hippocampal CA1 cells. J Physiol 512(Pt 1):61–73

  70. Lipscombe D, Helton TD, Xu W (2004) L-type calcium channels: the low down. J Neurophysiol 92:2633–2641

  71. Lodge DJ, Grace AA (2006) The laterodorsal tegmentum is essential for burst firing of ventral tegmental area dopamine neurons. Proc Natl Acad Sci USA 103:5167–5172

  72. Losonczy A, Biro AA, Nusser Z (2004) Persistently active cannabinoid receptors mute a subpopulation of hippocampal interneurons. Proc Natl Acad Sci USA 101:1362–1367

  73. Ludwig A, Flockerzi V, Hofmann F (1997) Regional expression and cellular localization of the alpha1 and beta subunit of high voltage-activated calcium channels in rat brain. J Neurosci 17:1339–1349

  74. Mackie K, Hille B (1992) Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc Natl Acad Sci USA 89:3825–3829

  75. Mackie K, Lai Y, Westenbroek R, Mitchell R (1995) Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. J Neurosci 15:6552–6561

  76. Maejima T, Hashimoto K, Yoshida T, Aiba A, Kano M (2001) Presynaptic inhibition caused by retrograde signal from metabotropic glutamate to cannabinoid receptors. Neuron 31:463–475

  77. Mailleux P, Vanderhaeghen JJ (1992) Distribution of neuronal cannabinoid receptor in the adult rat brain: a comparative receptor binding radioautography and in situ hybridization histochemistry. Neuroscience 48:655–668

  78. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564

  79. Matsuda LA, Bonner TI, Lolait SJ (1993) Localization of cannabinoid receptor mRNA in rat brain. J Comp Neurol 327:535–550

  80. Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR et al (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90

  81. Melis M, Pistis M, Perra S, Muntoni AL, Pillolla G, Gessa GL (2004) Endocannabinoids mediate presynaptic inhibition of glutamatergic transmission in rat ventral tegmental area dopamine neurons through activation of CB1 receptors. J Neurosci 24:53–62

  82. Min R, Di Marzo V, Mansvelder HD (2010) DAG lipase involvement in depolarization-induced suppression of inhibition: does endocannabinoid biosynthesis always meet the demand? Neuroscientist 16:608–613

  83. Morishita W, Alger BE (1997) Sr2+ supports depolarization-induced suppression of inhibition and provides new evidence for a presynaptic expression mechanism in rat hippocampal slices. J Physiol 505(Pt 2):307–317

  84. Morishita W, Kirov SA, Alger BE (1998) Evidence for metabotropic glutamate receptor activation in the induction of depolarization-induced suppression of inhibition in hippocampal CA1. J Neurosci 18:4870–4882

  85. Murphy TH, Baraban JM, Wier WG (1995) Mapping miniature synaptic currents to single synapses using calcium imaging reveals heterogeneity in postsynaptic output. Neuron 15:159–168

  86. Naraghi M (1997) T-jump study of calcium binding kinetics of calcium chelators. Cell Calcium 22:255–268

  87. Neher E (1992) Correction for liquid junction potentials in patch clamp experiments. Methods Enzymol 207:123–131

  88. Nelson CL, Wetter JB, Milovanovic M, Wolf ME (2007) The laterodorsal tegmentum contributes to behavioral sensitization to amphetamine. Neuroscience 146:41–49

  89. Neu A, Foldy C, Soltesz I (2007) Postsynaptic origin of CB1-dependent tonic inhibition of GABA release at cholecystokinin-positive basket cell to pyramidal cell synapses in the CA1 region of the rat hippocampus. J Physiol 578:233–247

  90. Nicholson AN, Turner C, Stone BM, Robson PJ (2004) Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. J Clin Psychopharmacol 24:305–313

  91. Norris CM, Halpain S, Foster TC (1998) Reversal of age-related alterations in synaptic plasticity by blockade of L-type Ca2+ channels. J Neurosci 18:3171–3179

  92. Ohno-Shosaku T, Shosaku J, Tsubokawa H, Kano M (2002) Cooperative endocannabinoid production by neuronal depolarization and group I metabotropic glutamate receptor activation. Eur J Neurosci 15:953–961

  93. Ohno-Shosaku T, Matsui M, Fukudome Y, Shosaku J, Tsubokawa H, Taketo MM, Manabe T, Kano M (2003) Postsynaptic M1 and M3 receptors are responsible for the muscarinic enhancement of retrograde endocannabinoid signalling in the hippocampus. Eur J Neurosci 18:109–116

  94. Ohno-Shosaku T, Hashimotodani Y, Maejima T, Kano M (2005) Calcium signaling and synaptic modulation: regulation of endocannabinoid-mediated synaptic modulation by calcium. Cell Calcium 38:369–374

  95. Omelchenko N, Sesack SR (2005) Laterodorsal tegmental projections to identified cell populations in the rat ventral tegmental area. J Comp Neurol 483:217–235

  96. Omelchenko N, Sesack SR (2006) Cholinergic axons in the rat ventral tegmental area synapse preferentially onto mesoaccumbens dopamine neurons. J Comp Neurol 494:863–875

  97. Oz M (2006a) Receptor-independent actions of cannabinoids on cell membranes: focus on endocannabinoids. Pharmacol Ther 111:114–144

  98. Oz M (2006b) Receptor-independent effects of endocannabinoids on ion channels. Curr Pharm Des 12:227–239

  99. Perra S, Pillolla G, Melis M, Muntoni AL, Gessa GL, Pistis M (2005) Involvement of the endogenous cannabinoid system in the effects of alcohol in the mesolimbic reward circuit: electrophysiological evidence in vivo. Psychopharmacology 183:368–377

  100. Pitler TA, Alger BE (1992) Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal pyramidal cells. J Neurosci 12:4122–4132

  101. Pivik RT, Zarcone V, Dement WC, Hollister LE (1972) Delta-9-tetrahydrocannabinol and synhexl: effects on human sleep patterns. Clin Pharmacol Ther 13:426–435

  102. Pontieri FE, Tanda G, Di Chiara G (1995) Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the “shell” as compared with the “core” of the rat nucleus accumbens. Proc Natl Acad Sci USA 92:12304–12308

  103. Puente N, Cui Y, Lassalle O, Lafourcade M, Georges F, Venance L, Grandes P, Manzoni OJ (2011) Polymodal activation of the endocannabinoid system in the extended amygdala. Nat Neurosci 14:1542–1547

  104. Regehr WG, Connor JA, Tank DW (1989) Optical imaging of calcium accumulation in hippocampal pyramidal cells during synaptic activation. Nature 341:533–536

  105. Rinaldi-Carmona M, Barth F, Heaulme M, Alonso R, Shire D, Congy C, Soubrie P, Breliere JC, Le Fur G (1995) Biochemical and pharmacological characterisation of SR141716A, the first potent and selective brain cannabinoid receptor antagonist. Life Sci 56:1941–1947

  106. Rivero-Rios P, Gomez-Suaga P, Fdez E, Hilfiker S (2014) Upstream deregulation of calcium signaling in Parkinson’s disease. Front Mol Neurosci 7:53

  107. Robbe D, Alonso G, Duchamp F, Bockaert J, Manzoni OJ (2001) Localization and mechanisms of action of cannabinoid receptors at the glutamatergic synapses of the mouse nucleus accumbens. J Neurosci 21:109–116

  108. Robbe D, Kopf M, Remaury A, Bockaert J, Manzoni OJ (2002) Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens. Proc Natl Acad Sci USA 99:8384–8388

  109. Robbe D, Alonso G, Manzoni OJ (2003) Exogenous and endogenous cannabinoids control synaptic transmission in mice nucleus accumbens. Ann N Y Acad Sci 1003:212–225

  110. Robbe D, Montgomery SM, Thome A, Rueda-Orozco PE, McNaughton BL, Buzsaki G (2006) Cannabinoids reveal importance of spike timing coordination in hippocampal function. Nat Neurosci 9:1526–1533

  111. Roberto M, Cruz M, Bajo M, Siggins GR, Parsons LH, Schweitzer P (2010) The endocannabinoid system tonically regulates inhibitory transmission and depresses the effect of ethanol in central amygdala. Neuropsychopharmacology 35:1962–1972

  112. Sargoy A, Sun X, Barnes S, Brecha NC (2014) Differential calcium signaling mediated by voltage-gated calcium channels in rat retinal ganglion cells and their unmyelinated axons. PLoS One 9:e84507

  113. Satoh K, Fibiger HC (1986) Cholinergic neurons of the laterodorsal tegmental nucleus: efferent and afferent connections. J Comp Neurol 253:277–302

  114. Serrano A, Parsons LH (2011) Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors. Pharmacol Ther 132:215–241

  115. Soni N, Satpathy S, Kohlmeier KA (2014) Neurophysiological Evidence for the Presence of Cannabinoid CB1 receptors in the Laterodorsal Tegmental Nucleus: a New Aspect of Neuronal Control of Marijuana Addiction and States of Arousal. Eur J Neurosci 40:3635–3652

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

  117. Straiker A, Sullivan JM (2003) Cannabinoid receptor activation differentially modulates ion channels in photoreceptors of the tiger salamander. J Neurophysiol 89:2647–2654

  118. Straiker A, Stella N, Piomelli D, Mackie K, Karten HJ, Maguire G (1999) Cannabinoid CB1 receptors and ligands in vertebrate retina: localization and function of an endogenous signaling system. Proc Natl Acad Sci USA 96:14565–14570

  119. Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K, Yamashita A, Waku K (1995) 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 215:89–97

  120. Sugiura T, Kodaka T, Kondo S, Nakane S, Kondo H, Waku K, Ishima Y, Watanabe K, Yamamoto I (1997) Is the cannabinoid CB1 receptor a 2-arachidonoylglycerol receptor? Structural requirements for triggering a Ca2+ transient in NG108-15 cells. J Biochem 122:890–895

  121. Sugiura T, Kodaka T, Nakane S, Miyashita T, Kondo S, Suhara Y, Takayama H, Waku K, Seki C, Baba N, Ishima Y (1999) Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds. J Biol Chem 274:2794–2801

  122. Takahashi A, Camacho P, Lechleiter JD, Herman B (1999) Measurement of intracellular calcium. Physiol Rev 79:1089–1125

  123. Takahashi N, Sasaki T, Usami A, Matsuki N, Ikegaya Y (2007) Watching neuronal circuit dynamics through functional multineuron calcium imaging (fMCI). Neurosci Res 58:219–225

  124. Thakkar MM, Strecker RE, McCarley RW (1998) Behavioral state control through differential serotonergic inhibition in the mesopontine cholinergic nuclei: a simultaneous unit recording and microdialysis study. J Neurosci 18:5490–5497

  125. Tsien RY (1980) New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures. Biochemistry 19:2396–2404

  126. Tsou K, Brown S, Sanudo-Pena MC, Mackie K, Walker JM (1998) Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 83:393–411

  127. Varma N, Carlson GC, Ledent C, Alger BE (2001) Metabotropic glutamate receptors drive the endocannabinoid system in hippocampus. J Neurosci 21:RC188

  128. Vincent SR, Satoh K, Armstrong DM, Fibiger HC (1983) NADPH-diaphorase: a selective histochemical marker for the cholinergic neurons of the pontine reticular formation. Neurosci Lett 43:31–36

  129. Wang HL, Morales M (2009) Pedunculopontine and laterodorsal tegmental nuclei contain distinct populations of cholinergic, glutamatergic and GABAergic neurons in the rat. Eur J Neurosci 29:340–358

  130. Wankerl K, Weise D, Gentner R, Rumpf JJ, Classen J (2010) L-type voltage-gated Ca2+ channels: a single molecular switch for long-term potentiation/long-term depression-like plasticity and activity-dependent metaplasticity in humans. J Neurosci 30:6197–6204

  131. Webster HH, Jones BE (1988) Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. II. Effects upon sleep-waking states. Brain Res 458:285–302

  132. Weisskopf MG, Bauer EP, LeDoux JE (1999) L-type voltage-gated calcium channels mediate NMDA-independent associative long-term potentiation at thalamic input synapses to the amygdala. J Neurosci 19:10512–10519

  133. Williams JA, Comisarow J, Day J, Fibiger HC, Reiner PB (1994) State-dependent release of acetylcholine in rat thalamus measured by in vivo microdialysis. J Neurosci 14:5236–5242

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

  135. Wilson RI, Kunos G, Nicoll RA (2001) Presynaptic specificity of endocannabinoid signaling in the hippocampus. Neuron 31:453–462

  136. Zhu PJ, Lovinger DM (2005) Retrograde endocannabinoid signaling in a postsynaptic neuron/synaptic bouton preparation from basolateral amygdala. J Neurosci 25:6199–6207

  137. Zweig RM, Jankel WR, Hedreen JC, Mayeux R, Price DL (1989) The pedunculopontine nucleus in Parkinson’s disease. Ann Neurol 26:41–46

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Acknowledgments

We acknowledge Mr. Jason Allen Teem for his excellent laboratory skills and assistance in the preparation of brain slices and conducting portions of the immunohistochemistry presented in this report. We would also like to express our thanks to the reviewers who suggested experiments that improved the MS. Funding for this work has been provided in part by a stipend to NS and equipment grants from the Drug Research Academy, funds from the University of Copenhagen and, in part, by a grant to KAK from the Philip Morris External Research Program.

Conflicts of interest

The authors disclose that they have no conflicts of interest with respect to this manuscript.

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Correspondence to Kristi A. Kohlmeier.

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Soni, N., Kohlmeier, K.A. Endocannabinoid CB1 receptor-mediated rises in Ca2+ and depolarization-induced suppression of inhibition within the laterodorsal tegmental nucleus. Brain Struct Funct 221, 1255–1277 (2016). https://doi.org/10.1007/s00429-014-0969-4

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Keywords

  • LDT
  • Marijuana
  • Synaptic transmission
  • Ca2+ imaging
  • DSI
  • mGluR