Endocannabinoid Mediated Long-Term Depression at Inhibitory Synapses

  • Chiayu Q. Chiu
  • Pablo E. Castillo


Long-lasting activity-dependent changes in synaptic strength, in the form of long-term potentiation (LTP) or depression (LTD), are thought to be the cellular basis of learning and memory. Although inhibitory synapses are critical for proper functioning of neural circuits, most of the studies investigating synaptic plasticity have concentrated on excitatory glutamatergic synapses. The idea that inhibitory synapses are plastic like excitatory synapses is gradually being accepted. Different forms of GABAergic synaptic plasticity have recently been reported. Among them, one of the most intensely studied is a form of LTD mediated by a group of retrograde messengers, collectively called endocannabinoids (eCBs). eCB-mediated LTD at inhibitory synapses (I-LTD) is a heterosynaptic form of plasticity, whose induction typically requires the activation of metabotropic glutamatergic receptors by nearby excitatory inputs and the resulting eCB mobilization from the postsynaptic cell. By activating presynaptic type 1 cannabinoid receptors (CB1Rs), eCBs can cause a long-lasting reduction in GABA release. I-LTD has been identified in several brain structures and may serve as a mechanism by which neurons adjust the strength of the inhibition they receive in response to excitatory afferent stimulation. In light of the wide-ranging effects of inhibition on synaptic transmission, from shaping the input-output relationship and excitability of neurons to modulating the inducibility of excitatory synaptic plasticity, I-LTD is expected to have significant impact on the excitatory/inhibitory balance within circuits and on neural network function. In this chapter, we review the main properties of eCB-mediated LTD at GABAergic synapses with the aim of understanding its physiological role.


Gaba Release Excitatory Synapse Inhibitory Synapse Theta Burst Stimulation Postsynaptic Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Supported by NIH/NIDA and by NARSAD. We thank Thomas Younts for critical reading of the manuscript.


  1. Abraham WC, Gustafsson B, Wigstrom H (1987) Long-term potentiation involves enhanced synaptic excitation relative to synaptic inhibition in guinea-pig hippocampus. J Physiol 394:367–380.PubMedGoogle Scholar
  2. Adermark L, Lovinger DM (2009) Frequency-dependent inversion of net striatal output by endocannabinoid-dependent plasticity at different synaptic inputs. J Neurosci 29:1375–1380.PubMedGoogle Scholar
  3. Adermark L, Talani G, Lovinger DM (2009) Endocannabinoid-dependent plasticity at GABAergic and glutamatergic synapses in the striatum is regulated by synaptic activity. Eur J Neurosci 29:32–41.PubMedGoogle Scholar
  4. Aigner TG (1988) Delta-9-tetrahydrocannabinol impairs visual recognition memory but not discrimination learning in rhesus monkeys. Psychopharmacology (Berl) 95:507–511.Google Scholar
  5. Alger BE (2002) Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids. Prog Neurobiol 68:247–286.PubMedGoogle Scholar
  6. Azad SC, Kurz J, Marsicano G, Lutz B, Zieglgansberger W, Rammes G (2008) Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the lateral amygdala. Learn Mem 15:143–152.PubMedGoogle Scholar
  7. Azad SC, Monory K, Marsicano G, Cravatt BF, Lutz B, Zieglgansberger W, Rammes G (2004) Circuitry for associative plasticity in the amygdala involves endocannabinoid signaling. J Neurosci 24:9953–9961.PubMedGoogle Scholar
  8. Balleine BW, Delgado MR, Hikosaka O (2007) The role of the dorsal striatum in reward and decision-making. J Neurosci 27:8161–8165.PubMedGoogle Scholar
  9. Barnes CA (1988) Spatial learning and memory processes: the search for their neurobiological mechanisms in the rat. Trends Neurosci 11:163–169.PubMedGoogle Scholar
  10. Beltramo M, Stella N, Calignano A, Lin SY, Makriyannis A, Piomelli D (1997) Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science 277:1094–1097.PubMedGoogle Scholar
  11. Bender VA, Bender KJ, Brasier DJ, Feldman DE (2006) Two coincidence detectors for spike timing-dependent plasticity in somatosensory cortex. J Neurosci 26:4166–4177.PubMedGoogle Scholar
  12. Best AR, Regehr WG (2008) Serotonin evokes endocannabinoid release and retrogradely suppresses excitatory synapses. J Neurosci 28:6508–6515.PubMedGoogle Scholar
  13. Bisogno T, MacCarrone M, De Petrocellis L, Jarrahian A, Finazzi-Agro A, Hillard C, Di Marzo V (2001) The uptake by cells of 2-arachidonoylglycerol, an endogenous agonist of cannabinoid receptors. Eur J Biochem 268:1982–1989.PubMedGoogle Scholar
  14. Bodor AL, Katona I, Nyiri G, Mackie K, Ledent C, Hajos N, Freund TF (2005) Endocannabinoid signaling in rat somatosensory cortex: laminar differences and involvement of specific interneuron types. J Neurosci 25:6845–6856.PubMedGoogle Scholar
  15. Brown SP, Brenowitz SD, Regehr WG (2003) Brief presynaptic bursts evoke synapse-specific retrograde inhibition mediated by endogenous cannabinoids. Nat Neurosci 6:1048–1057.PubMedGoogle Scholar
  16. Calabresi P, Picconi B, Tozzi A, Di Filippo M (2007) Dopamine-mediated regulation of corticostriatal synaptic plasticity. Trends Neurosci 30:211–219.PubMedGoogle Scholar
  17. Carlezon WA, Jr., Nestler EJ (2002) Elevated levels of GluR1 in the midbrain: a trigger for sensitization to drugs of abuse? Trends Neurosci 25:610–615.PubMedGoogle Scholar
  18. Castillo PE, Khodakhah K (2006) Biochemical confinements without walls in aspiny neurons. Nat Neurosci 9:719–720.PubMedGoogle Scholar
  19. Centonze D, Battista N, Rossi S, Mercuri NB, Finazzi-Agro A, Bernardi G, Calabresi P, Maccarrone M (2004) A critical interaction between dopamine D2 receptors and endocannabinoids mediates the effects of cocaine on striatal gabaergic Transmission. Neuropsychopharmacology 29:1488–1497.PubMedGoogle Scholar
  20. Chavez-Noriega LE, Bliss TV, Halliwell JV (1989) The EPSP-spike (E-S) component of long-term potentiation in the rat hippocampal slice is modulated by GABAergic but not cholinergic mechanisms. Neurosci Lett 104:58–64.PubMedGoogle Scholar
  21. Chevaleyre V, Castillo PE (2003) Heterosynaptic LTD of hippocampal GABAergic synapses: a novel role of endocannabinoids in regulating excitability. Neuron 38:461–472.PubMedGoogle Scholar
  22. Chevaleyre V, Castillo PE (2004) Endocannabinoid-mediated metaplasticity in the hippocampus. Neuron 43:871–881.PubMedGoogle Scholar
  23. Chevaleyre V, Takahashi KA, Castillo PE (2006) Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci 29:37–76.PubMedGoogle Scholar
  24. Chevaleyre V, Heifets BD, Kaeser PS, Sudhof TC, Castillo PE (2007) Endocannabinoid-mediated long-term plasticity requires cAMP/PKA signaling and RIM1alpha. Neuron 54:801–812.PubMedGoogle Scholar
  25. Chiu CQ, Puente N, Grandes P, Castillo PE (2010) Dopaminergic modulation of endocannabinoid-mediated plasticity at GABAergic synapses in the prefrontal cortex. J Neurosci. 30:7236–7248.Google Scholar
  26. Crozier RA, Wang Y, Liu CH, Bear MF (2007) Deprivation-induced synaptic depression by distinct mechanisms in different layers of mouse visual cortex. Proc Natl Acad Sci USA 104:1383–1388.PubMedGoogle Scholar
  27. 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.PubMedGoogle Scholar
  28. Di Marzo V, Fontana A, Cadas H, Schinelli S, Cimino G, Schwartz JC, Piomelli D (1994) Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372:686–691.PubMedGoogle Scholar
  29. Di Matteo V, Pierucci M, Di Giovanni G, Benigno A, Esposito E (2007) The neurobiological bases for the pharmacotherapy of nicotine addiction. Curr Pharm Des 13:1269–1284.PubMedGoogle Scholar
  30. Edwards DA, Kim J, Alger BE (2006) Multiple mechanisms of endocannabinoid response initiation in hippocampus. J Neurophysiol 95:67–75.PubMedGoogle Scholar
  31. Egertova M, Giang DK, Cravatt BF, Elphick MR (1998) A new perspective on cannabinoid signalling: complementary localization of fatty acid amide hydrolase and the CB1 receptor in rat brain. Proc Biol Sci 265:2081–2085.PubMedGoogle Scholar
  32. Ehrlich I, Humeau Y, Grenier F, Ciocchi S, Herry C, Luthi A (2009) Amygdala inhibitory circuits and the control of fear memory. Neuron 62:757–771.PubMedGoogle Scholar
  33. Ferrari F, Ottani A, Vivoli R, Giuliani D (1999) Learning impairment produced in rats by the cannabinoid agonist HU 210 in a water-maze task. Pharmacol Biochem Behav 64:555–561.PubMedGoogle Scholar
  34. Freund TF, Katona I, Piomelli D (2003) Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83:1017–1066.PubMedGoogle Scholar
  35. Galante M, Diana MA (2004) Group I metabotropic glutamate receptors inhibit GABA release at interneuron-Purkinje cell synapses through endocannabinoid production. J Neurosci 24:4865–4874.PubMedGoogle Scholar
  36. Gardner EL (2005) Endocannabinoid signaling system and brain reward: emphasis on dopamine. Pharmacol Biochem Behav 81:263–284.PubMedGoogle Scholar
  37. Gerdeman GL, Ronesi J, Lovinger DM (2002) Postsynaptic endocannabinoid release is critical to long-term depression in the striatum. Nat Neurosci 5:446–451.PubMedGoogle Scholar
  38. Giuffrida A, Parsons LH, Kerr TM, Rodriguez de Fonseca F, Navarro M, Piomelli D (1999) Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 2:358–363.PubMedGoogle Scholar
  39. Graybiel AM (1995) Building action repertoires: memory and learning functions of the basal ganglia. Curr Opin Neurobiol 5:733–741.PubMedGoogle Scholar
  40. Hampson RE, Deadwyler SA (1998) Role of cannabinoid receptors in memory storage. Neurobiol Dis 5:474–482.PubMedGoogle Scholar
  41. Hashimotodani Y, Ohno-Shosaku T, Kano M (2007) Ca(2+)-assisted receptor-driven endocannabinoid release: mechanisms that associate presynaptic and postsynaptic activities. Curr Opin Neurobiol 17:360–365.PubMedGoogle Scholar
  42. Heifets BD, Castillo PE (2009) Endocannabinoid signaling and long-term synaptic plasticity. Annu Rev Physiol 71:283–306.PubMedGoogle Scholar
  43. Heifets BD, Chevaleyre V, Castillo PE (2008) Interneuron activity controls endocannabinoid-mediated presynaptic plasticity through calcineurin. Proc Natl Acad Sci USA 105:10250–10255.PubMedGoogle Scholar
  44. Henneberger C, Redman SJ, Grantyn R (2007) Cortical efferent control of subcortical sensory neurons by synaptic disinhibition. Cereb Cortex 17:2039–2049.PubMedGoogle Scholar
  45. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC (1990) Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA 87:1932–1936.PubMedGoogle Scholar
  46. Howlett AC (2002) The cannabinoid receptors. Prostaglandins Other Lipid Mediat 68–69:619–631.PubMedGoogle Scholar
  47. 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.PubMedGoogle Scholar
  48. Jog MS, Kubota Y, Connolly CI, Hillegaart V, Graybiel AM (1999) Building neural representations of habits. Science 286:1745–1749.PubMedGoogle Scholar
  49. Kaeser PS, Kwon HB, Blundell J, Chevaleyre V, Morishita W, Malenka RC, Powell CM, Castillo PE, Sudhof TC (2008) RIM1alpha phosphorylation at serine-413 by protein kinase A is not required for presynaptic long-term plasticity or learning. Proc Natl Acad Sci USA 105:14680–14685.PubMedGoogle Scholar
  50. Kang-Park MH, Wilson WA, Kuhn CM, Moore SD, Swartzwelder HS (2007) Differential sensitivity of GABA A receptor-mediated IPSCs to cannabinoids in hippocampal slices from adolescent and adult rats. J Neurophysiol 98:1223–1230.PubMedGoogle Scholar
  51. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89:309–380.PubMedGoogle Scholar
  52. Katona I, Sperlagh B, Sik A, Kafalvi 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.PubMedGoogle Scholar
  53. Kauer JA (2004) Learning mechanisms in addiction: synaptic plasticity in the ventral tegmental area as a result of exposure to drugs of abuse. Annu Rev Physiol 66:447–475.PubMedGoogle Scholar
  54. Kreitzer AC, Malenka RC (2005) Dopamine modulation of state-dependent endocannabinoid release and long-term depression in the striatum. J Neurosci 25:10537–10545.PubMedGoogle Scholar
  55. Kreitzer AC, Malenka RC (2007) Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson’s disease models. Nature 445:643–647.PubMedGoogle Scholar
  56. Kreitzer AC, Malenka RC (2008) Striatal plasticity and basal ganglia circuit function. Neuron 60:543–554.PubMedGoogle Scholar
  57. Lafourcade M, Elezgarai I, Mato S, Bakiri Y, Grandes P, Manzoni OJ (2007) Molecular components and functions of the endocannabinoid system in mouse prefrontal cortex. PLoS One 2:e709.PubMedGoogle Scholar
  58. Lichtman AH, Dimen KR, Martin BR (1995) Systemic or intrahippocampal cannabinoid administration impairs spatial memory in rats. Psychopharmacology (Berl) 119:282–290.Google Scholar
  59. Ligresti A, Cascio MG, Di Marzo V (2005) Endocannabinoid metabolic pathways and enzymes. Curr Drug Targets CNS Neurol Disord 4:615–623.PubMedGoogle Scholar
  60. Lovinger DM (2008) Presynaptic modulation by endocannabinoids. Handb Exp Pharmacol: 435–477.Google Scholar
  61. Lu YM, Mansuy IM, Kandel ER, Roder J (2000) Calcineurin-mediated LTD of GABAergic inhibition underlies the increased excitability of CA1 neurons associated with LTP. Neuron 26:197–205.PubMedGoogle Scholar
  62. 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.PubMedGoogle Scholar
  63. Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44:5–21.PubMedGoogle Scholar
  64. Maren S, Quirk GJ (2004) Neuronal signalling of fear memory. Nat Rev Neurosci 5:844–852.PubMedGoogle Scholar
  65. Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgansberger W, Di Marzo V, Lutz B (2002) The endogenous cannabinoid system controls extinction of aversive memories. Nature 418:530–534.PubMedGoogle Scholar
  66. Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A, Azad SC, Cascio MG, Gutierrez SO, van der Stelt M, Lopez-Rodriguez ML, Casanova E, Schutz G, Zieglgansberger W, Di Marzo V, Behl C, Lutz B (2003) CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 302:84–88.PubMedGoogle Scholar
  67. Martin SJ, Grimwood PD, Morris RG (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23:649–711.PubMedGoogle Scholar
  68. 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.PubMedGoogle Scholar
  69. 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.PubMedGoogle Scholar
  70. Milner B, Penfield W (1955) The effect of hippocampal lesions on recent memory. Trans Am Neurol Assoc:42–48.Google Scholar
  71. Monory K, Blaudzun H, Massa F, Kaiser N, Lemberger T, Schutz G, Wotjak CT, Lutz B, Marsicano G (2007) Genetic dissection of behavioural and autonomic effects of Delta(9)-tetrahydrocannabinol in mice. PLoS Biol 5:e269.PubMedGoogle Scholar
  72. Monory K, Massa F, Egertova M, Eder M, Blaudzun H, Westenbroek R, Kelsch W, Jacob W, Marsch R, Ekker M, Long J, Rubenstein JL, Goebbels S, Nave KA, During M, Klugmann M, Wolfel B, Dodt HU, Zieglgansberger W, Wotjak CT, Mackie K, Elphick MR, Marsicano G, Lutz B (2006) The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron 51:455–466.PubMedGoogle Scholar
  73. Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65.PubMedGoogle Scholar
  74. Myers KM, Davis M (2007) Mechanisms of fear extinction. Mol Psychiatry 12:120–150.PubMedGoogle Scholar
  75. Nevian T, Sakmann B (2006) Spine Ca2+ signaling in spike-timing-dependent plasticity. J Neurosci 26:11001–11013.PubMedGoogle Scholar
  76. O′Keefe J (1999) Do hippocampal pyramidal cells signal non-spatial as well as spatial information? Hippocampus 9:352–364.PubMedGoogle Scholar
  77. Packard MG, Knowlton BJ (2002) Learning and memory functions of the Basal Ganglia. Annu Rev Neurosci 25:563–593.PubMedGoogle Scholar
  78. Pan B, Hillard CJ, Liu QS (2008a) Endocannabinoid signaling mediates cocaine-induced inhibitory synaptic plasticity in midbrain dopamine neurons. J Neurosci 28:1385–1397.PubMedGoogle Scholar
  79. Pan B, Hillard CJ, Liu QS (2008b) D2 dopamine receptor activation facilitates endocannabinoid-mediated long-term synaptic depression of GABAergic synaptic transmission in midbrain dopamine neurons via cAMP-protein kinase A signaling. J Neurosci 28:14018–14030.PubMedGoogle Scholar
  80. Penzo MA, Pena JL (2009) Endocannabinoid-mediated long-term depression in the avian midbrain expressed presynaptically and postsynaptically. J Neurosci 29:4131–4139.PubMedGoogle Scholar
  81. Piomelli D (2003) The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 4:873–884.PubMedGoogle Scholar
  82. Pisani A, Centonze D, Bernardi G, Calabresi P (2005) Striatal synaptic plasticity: implications for motor learning and Parkinson’s disease. Mov Disord 20:395–402.PubMedGoogle Scholar
  83. Puighermanal E, Marsicano G, Busquets-Garcia A, Lutz B, Maldonado R, Ozaita A (2009) Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling. Nat Neurosci 12:1152–1158.PubMedGoogle Scholar
  84. Ranganathan M, D Souza DC (2006) The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology (Berl) 188:425–444.Google Scholar
  85. 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.PubMedGoogle Scholar
  86. Rodrigues SM, Schafe GE, LeDoux JE (2004) Molecular mechanisms underlying emotional learning and memory in the lateral amygdala. Neuron 44:75–91.PubMedGoogle Scholar
  87. Safo PK, Regehr WG (2005) Endocannabinoids control the induction of cerebellar LTD. Neuron 48:647–659.PubMedGoogle Scholar
  88. Schultz W, Tremblay L, Hollerman JR (2003) Changes in behavior-related neuronal activity in the striatum during learning. Trends Neurosci 26:321–328.PubMedGoogle Scholar
  89. Seino S, Shibasaki T (2005) PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis. Physiol Rev 85:1303–1342.PubMedGoogle Scholar
  90. Self DW (2004) Regulation of drug-taking and -seeking behaviors by neuroadaptations in the mesolimbic dopamine system. Neuropharmacology 47 Suppl 1:242–255.PubMedGoogle Scholar
  91. Singla S, Kreitzer AC, Malenka RC (2007) Mechanisms for synapse specificity during striatal long-term depression. J Neurosci 27:5260–5264.PubMedGoogle Scholar
  92. Sjostrom PJ, Turrigiano GG, Nelson SB (2003) Neocortical LTD via coincident activation of presynaptic NMDA and cannabinoid receptors. Neuron 39:641–654.PubMedGoogle Scholar
  93. Smart D, Gunthorpe MJ, Jerman JC, Nasir S, Gray J, Muir AI, Chambers JK, Randall AD, Davis JB (2000) The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1). Br J Pharmacol 129:227–230.PubMedGoogle Scholar
  94. Soler-Llavina GJ, Sabatini BL (2006) Synapse-specific plasticity and compartmentalized signaling in cerebellar stellate cells. Nat Neurosci 9:798–806.PubMedGoogle Scholar
  95. Sugiura T, Kobayashi Y, Oka S, Waku K (2002) Biosynthesis and degradation of anandamide and 2-arachidonoylglycerol and their possible physiological significance. Prostaglandins Leukot Essent Fatty Acids 66:173–192.PubMedGoogle Scholar
  96. 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.PubMedGoogle Scholar
  97. Sullivan JM (2000) Cellular and molecular mechanisms underlying learning and memory impairments produced by cannabinoids. Learn Mem 7:132–139.PubMedGoogle Scholar
  98. Surmeier DJ, Ding J, Day M, Wang Z, Shen W (2007) D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci 30:228–235.PubMedGoogle Scholar
  99. Suzuki A, Josselyn SA, Frankland PW, Masushige S, Silva AJ, Kida S (2004) Memory reconsolidation and extinction have distinct temporal and biochemical signatures. J Neurosci 24:4787–4795.PubMedGoogle Scholar
  100. Tzounopoulos T, Rubio ME, Keen JE, Trussell LO (2007) Coactivation of pre- and postsynaptic signaling mechanisms determines cell-specific spike-timing-dependent plasticity. Neuron 54:291–301.PubMedGoogle Scholar
  101. Uchigashima M, Narushima M, Fukaya M, Katona I, Kano M, Watanabe M (2007) Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its physiological contribution to synaptic modulation in the striatum. J Neurosci 27:3663–3676.PubMedGoogle Scholar
  102. Varvel SA, Lichtman AH (2002) Evaluation of CB1 receptor knockout mice in the Morris water maze. J Pharmacol Exp Ther 301:915–924.PubMedGoogle Scholar
  103. Varvel SA, Hamm RJ, Martin BR, Lichtman AH (2001) Differential effects of delta 9-THC on spatial reference and working memory in mice. Psychopharmacology (Berl) 157:142–150.Google Scholar
  104. Wilson RI, Kunos G, Nicoll RA (2001) Presynaptic specificity of endocannabinoid signaling in the hippocampus. Neuron 31:453–462.PubMedGoogle Scholar
  105. Yasuda H, Huang Y, Tsumoto T (2008) Regulation of excitability and plasticity by endocannabinoids and PKA in developing hippocampus. Proc Natl Acad Sci USA 105:3106–3111.PubMedGoogle Scholar
  106. Yin HH, Lovinger DM (2006) Frequency-specific and D2 receptor-mediated inhibition of glutamate release by retrograde endocannabinoid signaling. Proc Natl Acad Sci USA 103:8251–8256.PubMedGoogle Scholar
  107. Zhu PJ, Lovinger DM (2007) Persistent synaptic activity produces long-lasting enhancement of endocannabinoid modulation and alters long-term synaptic plasticity. J Neurophysiol 97:4386–4389.PubMedGoogle Scholar
  108. Zimmerberg B, Glick SD, Jarvik ME (1971) Impairment of recent memory by marihuana and THC in rhesus monkeys. Nature 233:343–345.PubMedGoogle Scholar
  109. 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.PubMedGoogle Scholar
  110. * During the editorial process, a report of eCB-mediated LTD at GABAergic synapses in the prefrontal cortex appeared (Chiu et al., 2010).Google Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Dominick P. Purpura Department of NeuroscienceAlbert Einstein College of MedicineBronxUSA

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