Skip to main content
SpringerLink
Log in

Cannabinoids and Synaptic Transmission in the Cerebellum

  • Reference work entry
Handbook of the Cerebellum and Cerebellar Disorders

Abstract

Endocannabinoids (eCBs) are retrograde messengers that regulate the strength of synapses throughout the brain. eCB signaling is prominent within the cerebellar cortex, where multiple types of neurons release eCBs in a calcium-dependent manner. Liberated eCBs suppress synaptic strength on both short and long timescales by retrogradely activating CB1 cannabinoid receptors (CB1Rs) on presynaptic terminals. The chapter will discuss mechanisms that control eCB release, the consequences of eCB signaling in the cerebellar cortex and the role of the eCB system in cerebellar function.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Aiba A, Kano M, Chen C, Stanton ME, Fox GD, Herrup K, Zwingman TA, Tonegawa S (1994) Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice. Cell 79:377–388

    Article  PubMed  CAS  Google Scholar 

  • Bacci A, Huguenard JR, Prince DA (2004) Long-lasting self-inhibition of neocortical interneurons mediated by endocannabinoids. Nature 431:312–316

    Article  PubMed  CAS  Google Scholar 

  • Beierlein M, Regehr WG (2006) Local interneurons regulate synaptic strength by retrograde release of endocannabinoids. J Neurosci 26:9935–9943

    Article  PubMed  CAS  Google Scholar 

  • Beierlein M, Fioravante D, Regehr WG (2007) Differential expression of posttetanic potentiation and retrograde signaling mediate target-dependent short-term synaptic plasticity. Neuron 54:949–959

    Article  PubMed  CAS  Google Scholar 

  • Best AR, Regehr WG (2008) Serotonin evokes endocannabinoid release and retrogradely suppresses excitatory synapses. J Neurosci 28:6508–6515

    Article  PubMed  CAS  Google Scholar 

  • Bouaboula M, Poinot-Chazel C, Bourrie B, Canat X, Calandra B, Rinaldi-Carmona M, Le Fur G, Casellas P (1995) Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. Biochem J 312(Pt 2):637–641

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Brenowitz SD, Regehr WG (2005) Associative short-term synaptic plasticity mediated by endocannabinoids. Neuron 45:419–431

    Article  PubMed  CAS  Google Scholar 

  • Brenowitz SD, Best AR, Regehr WG (2006) Sustained elevation of dendritic calcium evokes widespread endocannabinoid release and suppression of synapses onto cerebellar Purkinje cells. J Neurosci 26:6841–6850

    Article  PubMed  CAS  Google Scholar 

  • Brown SP, Brenowitz SD, Regehr WG (2003) Brief presynaptic bursts evoke synapse-specific retrograde inhibition mediated by endogenous cannabinoids. Nat Neurosci 6:1048–1057

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Cadas H, di Tomaso E, Piomelli D (1997) Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain. J Neurosci 17:1226–1242

    PubMed  CAS  Google Scholar 

  • Carey MR, Myoga MH, McDaniels KR, Marsicano G, Lutz B, Mackie K, Regehr WG (2010) Presynaptic CB1 receptors regulate synaptic plasticity at cerebellar parallel fiber synapses. J Neurophysiol 105:958–963

    Article  PubMed  CAS  Google Scholar 

  • Chavez AE, Chiu CQ, Castillo PE (2010) TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus. Nat Neurosci 13:1511–1518

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Regehr WG (1997) The mechanism of cAMP-mediated enhancement at a cerebellar synapse. J Neurosci 17:8687–8694

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Chevaleyre V, Takahashi KA, Castillo PE (2006) Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci 29:37–76

    Article  PubMed  CAS  Google Scholar 

  • Colleran K, Pai H (2007) Rimonabant: a novel approach for the treatment of obesity and cardiometabolic risk by blockade of the endocannabinoid system. Future Cardiol 3:497–505

    Article  PubMed  CAS  Google Scholar 

  • Cravatt BF, Giang DK, Mayfield SP, Boger DL, Lerner RA, Gilula NB (1996) Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384:83–87

    Article  PubMed  CAS  Google Scholar 

  • Cravatt BF, Demarest K, Patricelli MP, Bracey MH, Giang DK, Martin BR, Lichtman AH (2001) Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA 98:9371–9376

    Article  PubMed  CAS  Google Scholar 

  • Cristino L, Starowicz K, De Petrocellis L, Morishita J, Ueda N, Guglielmotti V, Di Marzo V (2008) Immunohistochemical localization of anabolic and catabolic enzymes for anandamide and other putative endovanilloids in the hippocampus and cerebellar cortex of the mouse brain. Neuroscience 151:955–968

    Article  PubMed  CAS  Google Scholar 

  • Daniel H, Levenes C, Crepel F (1998) Cellular mechanisms of cerebellar LTD. Trends Neurosci 21:401–407

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi SL, Kathuria S, Piomelli D (2002) Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 99:10819–10824

    Article  PubMed  CAS  Google Scholar 

  • Dittman JS, Regehr WG (1996) Contributions of calcium-dependent and calcium-independent mechanisms to presynaptic inhibition at a cerebellar synapse. J Neurosci 16:1623–1633

    PubMed  CAS  Google Scholar 

  • Egertova M, Elphick MR (2000) Localisation of cannabinoid receptors in the rat brain using antibodies to the intracellular C-terminal tail of CB. J Comp Neurol 422:159–171

    Article  PubMed  CAS  Google Scholar 

  • Gerdeman GL, Ronesi J, Lovinger DM (2002) Postsynaptic endocannabinoid release is critical to long-term depression in the striatum. Nat Neurosci 5:446–451

    PubMed  CAS  Google Scholar 

  • Grueter BA, Brasnjo G, Malenka RC (2010) Postsynaptic TRPV1 triggers cell type-specific long-term depression in the nucleus accumbens. Nat Neurosci 13:1519–1525

    Article  PubMed  CAS  Google Scholar 

  • Gulyas AI, Cravatt BF, Bracey MH, Dinh TP, Piomelli D, Boscia F, Freund TF (2004) Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala. Eur J Neurosci 20:441–458

    Article  PubMed  CAS  Google Scholar 

  • Hanus L, Gopher A, Almog S, Mechoulam R (1993) Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor. J Med Chem 36:3032–3034

    Article  PubMed  CAS  Google Scholar 

  • Hanus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, Shalev DE, Kustanovich I, Mechoulam R (2001) 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci USA 98:3662–3665

    Article  PubMed  CAS  Google Scholar 

  • Hashimotodani Y, Ohno-Shosaku T, Tsubokawa H, Ogata H, Emoto K, Maejima T, Araishi K, Shin HS, Kano M (2005) Phospholipase Cbeta serves as a coincidence detector through its Ca2+ dependency for triggering retrograde endocannabinoid signal. Neuron 45:257–268

    Article  PubMed  CAS  Google Scholar 

  • Heishman SJ, Huestis MA, Henningfield JE, Cone EJ (1990) Acute and residual effects of marijuana: profiles of plasma THC levels, physiological, subjective, and performance measures. Pharmacol Biochem Behav 37:561–565

    Article  PubMed  CAS  Google Scholar 

  • Henry DJ, Chavkin C (1995) Activation of inwardly rectifying potassium channels (GIRK1) by co-expressed rat brain cannabinoid receptors in Xenopus oocytes. Neurosci Lett 186:91–94

    Article  PubMed  CAS  Google Scholar 

  • Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC (1991) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 11:563–583

    PubMed  CAS  Google Scholar 

  • Hillard CJ, Muthian S, Kearn CS (1999) Effects of CB(1) cannabinoid receptor activation on cerebellar granule cell nitric oxide synthase activity. FEBS Lett 459:277–281

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Ito M (1989) Long-term depression. Annu Rev Neurosci 12:85–102

    Article  PubMed  CAS  Google Scholar 

  • Ito M (2001) Cerebellar long-term depression: characterization, signal transduction, and functional roles. Physiol Rev 81:1143–1195

    PubMed  CAS  Google Scholar 

  • Janowsky DS, Meacham MP, Blaine JD, Schoor M, Bozzetti LP (1976) Marijuana effects on simulated flying ability. Am J Psychiatry 133:384–388

    PubMed  CAS  Google Scholar 

  • Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89:309–380

    Article  PubMed  CAS  Google Scholar 

  • Kishimoto Y, Kano M (2006) Endogenous cannabinoid signaling through the CB1 receptor is essential for cerebellum-dependent discrete motor learning. J Neurosci 26:8829–8837

    Article  PubMed  CAS  Google Scholar 

  • Kreitzer AC, Malenka RC (2005) Dopamine modulation of state-dependent endocannabinoid release and long-term depression in the striatum. J Neurosci 25:10537–10545

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Kreitzer AC, Regehr WG (2001b) Cerebellar depolarization-induced suppression of inhibition is mediated by endogenous cannabinoids. J Neurosci 21:RC174

    PubMed  CAS  Google Scholar 

  • Kreitzer AC, Carter AG, Regehr WG (2002) Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. Neuron 34:787–796

    Article  PubMed  CAS  Google Scholar 

  • Lev-Ram V, Jiang T, Wood J, Lawrence DS, Tsien RY (1997) Synergies and coincidence requirements between NO, cGMP, and Ca2+ in the induction of cerebellar long-term depression. Neuron 18:1025–1038

    Article  PubMed  CAS  Google Scholar 

  • Liguori A, Gatto CP, Robinson JH (1998) Effects of marijuana on equilibrium, psychomotor performance, and simulated driving. Behav Pharmacol 9:599–609

    Article  PubMed  CAS  Google Scholar 

  • 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 6:565–574

    Article  PubMed  CAS  Google Scholar 

  • Mackie K (2005) Distribution of cannabinoid receptors in the central and peripheral nervous system. Handb Exp Pharmacol 168:299–325

    Article  PubMed  CAS  Google Scholar 

  • Mackie K (2008) Cannabinoid receptors: where they are and what they do. J Neuroendocrinol 20(Suppl 1):10–14

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Maeda H, Ellis-Davies GC, Ito K, Miyashita Y, Kasai H (1999) Supralinear Ca2+ signaling by cooperative and mobile Ca2+ buffering in Purkinje neurons. Neuron 24:989–1002

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Maejima T, Oka S, Hashimotodani Y, Ohno-Shosaku T, Aiba A, Wu D, Waku K, Sugiura T, Kano M (2005) Synaptically driven endocannabinoid release requires Ca2+ −assisted metabotropic glutamate receptor subtype 1 to phospholipase Cbeta4 signaling cascade in the cerebellum. J Neurosci 25:6826–6835

    Article  PubMed  CAS  Google Scholar 

  • Marinelli S, Pacioni S, Bisogno T, Di Marzo V, Prince DA, Huguenard JR, Bacci A (2008) The endocannabinoid 2-arachidonoylglycerol is responsible for the slow self-inhibition in neocortical interneurons. J Neurosci 28:13532–13541

    Article  PubMed  CAS  Google Scholar 

  • Martina M, Metz AE, Bean BP (2007) Voltage-dependent potassium currents during fast spikes of rat cerebellar Purkinje neurons: inhibition by BDS-I toxin. J Neurophysiol 97:563–571

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Mechoulam R, Gaoni Y (1965) A total synthesis of DL-delta-1-tetrahydrocannabinol, the active constituent of hashish. J Am Chem Soc 87:3273–3275

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Miyata M, Kim HT, Hashimoto K, Lee TK, Cho SY, Jiang H, Wu Y, Jun K, Wu D, Kano M, Shin HS (2001) Deficient long-term synaptic depression in the rostral cerebellum correlated with impaired motor learning in phospholipase C beta4 mutant mice. Eur J Neurosci 13:1945–1954

    Article  PubMed  CAS  Google Scholar 

  • Moreira FA, Crippa JA (2009) The psychiatric side-effects of rimonabant. Rev Bras Psiquiatr 31:145–153

    Article  PubMed  Google Scholar 

  • Myoga MH, Beierlein M, Regehr WG (2009) Somatic spikes regulate dendritic signaling in small neurons in the absence of backpropagating action potentials. J Neurosci 29:7803–7814

    Article  PubMed  CAS  Google Scholar 

  • Myoga MH, Regehr WG (2011) Calcium microdomains near R-type calcium channels control the induction of presynaptic long-term potentiation at parallel fiber to purkinje cell synapses. J Neurosci 31:5235–5243

    Article  PubMed  CAS  Google Scholar 

  • Nakamura M, Sato K, Fukaya M, Araishi K, Aiba A, Kano M, Watanabe M (2004) Signaling complex formation of phospholipase Cbeta4 with metabotropic glutamate receptor type 1alpha and 1,4,5-trisphosphate receptor at the perisynapse and endoplasmic reticulum in the mouse brain. Eur J Neurosci 20:2929–2944

    Article  PubMed  Google Scholar 

  • Neher E, Sakaba T (2008) Multiple roles of calcium ions in the regulation of neurotransmitter release. Neuron 59:861–872

    Article  PubMed  CAS  Google Scholar 

  • Offermanns S, Hashimoto K, Watanabe M, Sun W, Kurihara H, Thompson RF, Inoue Y, Kano M, Simon MI (1997) Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Galphaq. Proc Natl Acad Sci USA 94:14089–14094

    Article  PubMed  CAS  Google Scholar 

  • Ohno-Shosaku T, Maejima T, Kano M (2001) Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals. Neuron 29:729–738

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Palay SL, Chan-Palay V (1974) Cerebellar cortex. Springer, New York

    Book  Google Scholar 

  • Pang DS, Robledo CJ, Carr DR, Gent TC, Vyssotski AL, Caley A, Zecharia AY, Wisden W, Brickley SG, Franks NP (2009) An unexpected role for TASK-3 potassium channels in network oscillations with implications for sleep mechanisms and anesthetic action. Proc Natl Acad Sci USA 106:17546–17551

    Article  PubMed  CAS  Google Scholar 

  • Pertwee RG (2007) GPR55: a new member of the cannabinoid receptor clan? Br J Pharmacol 152:984–986

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Raymond JL, Lisberger SG, Mauk MD (1996) The cerebellum: a neuronal learning machine? Science 272:1126–1131

    Article  PubMed  CAS  Google Scholar 

  • Rebecchi MJ, Pentyala SN (2000) Structure, function, and control of phosphoinositide-specific phospholipase C. Physiol Rev 80:1291–1335

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Ronesi J, Gerdeman GL, Lovinger DM (2004) Disruption of endocannabinoid release and striatal long-term depression by postsynaptic blockade of endocannabinoid membrane transport. J Neurosci 24:1673–1679

    Article  PubMed  CAS  Google Scholar 

  • Safo PK, Regehr WG (2005) Endocannabinoids control the induction of cerebellar LTD. Neuron 48:647–659

    Article  PubMed  CAS  Google Scholar 

  • Safo PK, Cravatt BF, Regehr WG (2006) Retrograde endocannabinoid signaling in the cerebellar cortex. Cerebellum 5:134–145

    Article  PubMed  CAS  Google Scholar 

  • Salin PA, Malenka RC, Nicoll RA (1996) Cyclic AMP mediates a presynaptic form of LTP at cerebellar parallel fiber synapses. Neuron 16:797–803

    Article  PubMed  CAS  Google Scholar 

  • Sawzdargo M, Nguyen T, Lee DK, Lynch KR, Cheng R, Heng HH, George SR, O’Dowd BF (1999) Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain. Brain Res Mol Brain Res 64:193–198

    Article  PubMed  CAS  Google Scholar 

  • Schlicker E, Kathmann M (2001) Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol Sci 22:565–572

    Article  PubMed  CAS  Google Scholar 

  • Schonewille M, Belmeguenai A, Koekkoek SK, Houtman SH, Boele HJ, van Beugen BJ, Gao Z, Badura A, Ohtsuki G, Amerika WE, Hosy E, Hoebeek FE, Elgersma Y, Hansel C, De Zeeuw CI (2010) Purkinje cell-specific knockout of the protein phosphatase PP2B impairs potentiation and cerebellar motor learning. Neuron 67:618–628

    Article  PubMed  CAS  Google Scholar 

  • Shibuki K, Okada D (1991) Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum. Nature 349:326–328

    Article  PubMed  CAS  Google Scholar 

  • Sjostrom PJ, Turrigiano GG, Nelson SB (2003) Neocortical LTD via coincident activation of presynaptic NMDA and cannabinoid receptors. Neuron 39:641–654

    Article  PubMed  Google Scholar 

  • Skosnik PD, Edwards CR, O’Donnell BF, Steffen A, Steinmetz JE, Hetrick WP (2008) Cannabis use disrupts eyeblink conditioning: evidence for cannabinoid modulation of cerebellar-dependent learning. Neuropsychopharmacology 33:1432–1440

    Article  PubMed  CAS  Google Scholar 

  • Soler-Llavina GJ, Sabatini BL (2006) Synapse-specific plasticity and compartmentalized signaling in cerebellar stellate cells. Nat Neurosci 9:798–806

    Article  PubMed  CAS  Google Scholar 

  • Stella N, Schweitzer P, Piomelli D (1997) A second endogenous cannabinoid that modulates long-term potentiation. Nature 388:773–778

    Article  PubMed  CAS  Google Scholar 

  • Storm DR, Hansel C, Hacker B, Parent A, Linden DJ (1998) Impaired cerebellar long-term potentiation in type I adenylyl cyclase mutant mice. Neuron 20:1199–1210

    Article  PubMed  CAS  Google Scholar 

  • Suarez J, Bermudez-Silva FJ, Mackie K, Ledent C, Zimmer A, Cravatt BF, de Fonseca FR (2008) Immunohistochemical description of the endogenous cannabinoid system in the rat cerebellum and functionally related nuclei. J Comp Neurol 509:400–421

    Article  PubMed  CAS  Google Scholar 

  • Suhara Y, Takayama H, Nakane S, Miyashita T, Waku K, Sugiura T (2000) Synthesis and biological activities of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, and its metabolically stable ether-linked analogues. Chem Pharm Bull 48:903–907

    Article  PubMed  CAS  Google Scholar 

  • Tanimura A, Yamazaki M, Hashimotodani Y, Uchigashima M, Kawata S, Abe M, Kita Y, Hashimoto K, Shimizu T, Watanabe M, Sakimura K, Kano M (2010) The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission. Neuron 65:320–327

    Article  PubMed  CAS  Google Scholar 

  • van Beugen BJ, Nagaraja RY, Hansel C (2006) Climbing fiber-evoked endocannabinoid signaling heterosynaptically suppresses presynaptic cerebellar long-term potentiation. J Neurosci 26:8289–8294

    Article  PubMed  CAS  Google Scholar 

  • Vincent P, Marty A (1993) Neighboring cerebellar Purkinje cells communicate via retrograde inhibition of common presynaptic interneurons. Neuron 11:885–893

    Article  PubMed  CAS  Google Scholar 

  • Wang SS, Denk W, Hausser M (2000) Coincidence detection in single dendritic spines mediated by calcium release. Nat Neurosci 3:1266–1273

    Article  PubMed  CAS  Google Scholar 

  • Wang H, Pineda VV, Chan GC, Wong ST, Muglia LJ, Storm DR (2003) Type 8 adenylyl cyclase is targeted to excitatory synapses and required for mossy fiber long-term potentiation. J Neurosci 23:9710–9718

    PubMed  CAS  Google Scholar 

  • Wayman GA, Impey S, Wu Z, Kindsvogel W, Prichard L, Storm DR (1994) Synergistic activation of the type I adenylyl cyclase by Ca2+ and Gs-coupled receptors in vivo. J Biol Chem 269:25400–25405

    PubMed  CAS  Google Scholar 

  • Weisskopf MG, Castillo PE, Zalutsky RA, Nicoll RA (1994) Mediation of hippocampal mossy fiber long-term potentiation by cyclic AMP. Science 265:1878–1882

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Wong ST, Athos J, Figueroa XA, Pineda VV, Schaefer ML, Chavkin CC, Muglia LJ, Storm DR (1999) Calcium-stimulated adenylyl cyclase activity is critical for hippocampus-dependent long-term memory and late phase LTP. Neuron 23:787–798

    Article  PubMed  CAS  Google Scholar 

  • Yoshida T, Fukaya M, Uchigashima M, Miura E, Kamiya H, Kano M, Watanabe M (2006) Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor. J Neurosci 26:4740–4751

    Article  PubMed  CAS  Google Scholar 

  • Zalutsky RA, Nicoll RA (1990) Comparison of two forms of long-term potentiation in single hippocampal neurons. Science 248:1619–1624

    Article  PubMed  CAS  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 96:5780–5785

    Article  PubMed  CAS  Google Scholar 

  • Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sorgard M, Di Marzo V, Julius D, Hogestatt ED (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400:452–457

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA, 02115, USA

    Dr. Michael H. Myoga & Dr. Wade G. Regehr

Authors
  1. Dr. Michael H. Myoga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dr. Wade G. Regehr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wade G. Regehr .

Editor information

Editors and Affiliations

  1. Unité d'Etude du Mouvement (UEM), FNRS, Neurologie ULB Erasme, Bruxelles, Belgium

    Mario Manto

  2. Ataxia Unit, Cognitive and Behavioral Neurology Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Jeremy D. Schmahmann

  3. Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Orbassano, Turin, Italy

    Ferdinando Rossi

  4. Molecular and Integrative Neuroscience Department (MIND), The Scripps Research Institute, California, CA, USA

    Donna L. Gruol

  5. Department of Integrative Physiolgy, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Noriyuki Koibuchi

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Myoga, M.H., Regehr, W.G. (2013). Cannabinoids and Synaptic Transmission in the Cerebellum. In: Manto, M., Schmahmann, J.D., Rossi, F., Gruol, D.L., Koibuchi, N. (eds) Handbook of the Cerebellum and Cerebellar Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1333-8_39

Download citation

Publish with us

Policies and ethics

Search

Navigation