Cerebellar-Dependent learning as a neurobehavioral index of the cannabinoid system

Critical Reviews in Neurobiology

Volumn 19, Issue 1, 2007, Pages 29-57

  Edwards, Chad R ^a   Skosnik, Patrick D ^a  

^a INDIANA UNIVERSITY   (United States)

Author keywords

CB1; Cerebellum; EBC; Eyeblink conditioning; THC

Indexed keywords

ANANDAMIDE; CANNABINOID; CANNABINOID 1 RECEPTOR; ENDOCANNABINOID;

BRAIN FUNCTION; CELL FUNCTION; CEREBELLUM CORTEX; EYELID REFLEX; HUMAN; LEARNING; LONG TERM DEPRESSION; NONHUMAN; PROTEIN LOCALIZATION; PURKINJE CELL; REVIEW; SCHIZOPHRENIA; ANIMAL; BRAIN CORTEX; CONDITIONED REFLEX; CONDITIONING; CYTOLOGY; DRUG EFFECT; LONG TERM POTENTIATION; PHYSIOLOGY; SYNAPSE;

ANIMALS; CEREBRAL CORTEX; CONDITIONING, CLASSICAL; CONDITIONING, EYELID; ENDOCANNABINOIDS; HUMANS; LONG-TERM POTENTIATION; SYNAPSES;

EID: 64249092505     PISSN: 08920915     EISSN: None     Source Type: Journal    
DOI: 10.1615/critrevneurobiol.v19.i1.30     Document Type: Review

References (129)

1. Wright D, Sathe N, Spagnola K. State estimates of substance use from the 2004-2005 National Surveys on Drug Use and Health (DHHS Publication No. SMA 07-4235, NSDUH Series H-31). Rockville (MD): Substance Abuse and Mental Health Services Administration, Office of Applied Studies; 2007.
2. Ong WY, Mackie K. A light and electron microscopic study of the CB1 cannabinoid receptor in primate brain. Neuroscience. 1999;92(4):1177-91.
3. Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci. 1991; 11(2):563-83.
4. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A. 1990;87(5):1932-6.
5. Eggan SM, Lewis DA. Immunocytochemical distribution of the cannabinoid CB1 receptor in the primate neocortex: a regional and laminar analysis. Cereb Cortex. 2007;17(1):175-91.
6. Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, Vogt LJ, SimSelley LJ. Chronic delta-9-tetrahydrocannabinol treatment produces a time-dependent loss of cannabinoid receptors and cannabinoid receptoractivated G proteins in rat brain. J Neurochem. 1999;73(6):2447-59.
7. Villares J. Chronic use of marijuana decreases cannabinoid receptor binding and mRNA expression in the human brain. Neuroscience. 2007; 145(1):323-34.
8. Solowij N. Cannabis and cognitive functioning. Cambridge (UK): Cambridge University Press; 1998.
9. Pope HG Jr, Gruber AJ, Hudson JI, Huestis MA, Yurgelun-Todd D. Neuropsychological performance in long-term cannabis users. Arch Gen Psychiatry. 2001;58(10):909-15.
10. Ashton CH, Moore PB, Gallagher P, Young AH. Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential. J Psychopharmacol (Oxf). 2005;19(3):293-300.
11. Skosnik PD. Cannabis use increases risk of developing symptoms of mania. Br Med J. 2007;10(2):61.
12. Patton GC, Coffey C, Carlin JB, Degenhardt L, Lynskey M, Hall W. Cannabis use and mental health in young people: cohort study. BMJ. 2002;325(7374):1195- 8.
13. Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rössner S. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. The Lancet. 2005;365(9468):1389-97.
14. Siegfried Z, Kanyas K, Latzer Y, Karni O, Bloch M, Lerer B, Berry EM. Association study of cannabinoid receptor gene (CNR1) alleles and anorexia nervosa: differences between restricting and bingeing/purging subtypes. Am J Med Genet Part B. 2004;125(1):126-30.
15. Andreasson S, Allebeck P, Rydberg U. A longitudinal study in Stockholm County. Acta Psychiatr Scand. 1989;79(5):505-10.
16. Bersani G, Orlandi V, Kotzalidis GD, Pancheri P. Cannabis and schizophrenia: impact on onset, course, psychopathology and outcomes. Eur Arch Psychiatry Clin Neurosci. 2002;252(2):86-92.
17. Emrich HM, Leweke FM, Schneider U. Towards a cannabinoid hypothesis of schizophrenia: cognitive impairments due to dysregulation of the endogenous cannabinoid system. Pharmacol Biochem Behav. 1997;56(4): 803-7.
18. Linszen DH, Dingemans PM, Lenior ME. Cannabis abuse and the course of recent-onset schizophrenic disorders. Arch Gen Psychiatry. 1994;51(4): 273-9.
19. Skosnik PD, Yao JK. From membrane phospholipid defects to altered neurotransmission: is arachidonic acid a nexus in the pathophysiology of schizophrenia? Prostaglandins Leukot Essent Fatty Acids. 2003;69(6): 367-84.
20. Skosnik PD, Krishnan GP, Aydt EE, Kuhlenshmidt HA, O'Donnell BF. Psychophysiological evidence of altered neural synchronization in cannabis use: relationship to schizotypy. Am J Psychiatry. 2006;163(10): 1798-1805.
21. Ujike H, Morita Y. New perspectives in the studies on endocannabinoid and cannabis: cannabinoid receptors and schizophrenia. J Pharmacol Sci. 2004;96(4):376-81.
22. Madsen MV, Peacock L, Werge T, Andersen MB. Effects of the cannabinoid CB1 receptor agonist CP55, 940 and antagonist SR141716A on damphetamine-induced behaviours in Cebus monkeys. J Psychopharmacol (Oxf). 2006;20(5):622-8.
23. Meltzer HY, Arvanitis L, Bauer D, Rein W. Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am J Psychiatry. 2004;161(6):975-84.
24. Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. Int J Geriatr Psychiatry. 1997;12(9):913-9.
25. Zuardi AW, Crippa JAS, Hallak JEC, Moreira FA, Guimarães FS. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res. 2006;39:421-9.
26. Pertwee RG. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther. 1997;74(2):129-80.
27. Hájos N, Ledent C, Freund TF. Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. Neuroscience. 2001;106(1):1-4.
28. Begg M, Pacher P, Bátkai S, Osei-Hyiaman D, Offertáler L, Mo FM, Liu J, Kunos G. Evidence for novel cannabinoid receptors. Pharmacol Ther. 2005;106(2):133-45.
29. Iversen L. Cannabis and the brain. Brain. 2003;126(6):1252-70.
30. De Jesús ML, Sallés J, Meana JJ, Callado LF. Characterization of CB1 cannabinoid receptor immunoreactivity in postmortem human brain homogenates. Neuroscience. 2006;140(2):635-43.
31. Horti AG, Fan H, Kuwabara H, Hilton J, Ravert HT, Holt DP, Alexander M, Kumar A, Rahmim A, Scheffel U. 11C-JHU75528: a radiotracer for PET imaging of CB1 cannabinoid receptors. J Nucl Med. 2006;47(10):1689-96.
32. Van Laere K, Goffin K, Casteels C, Dupont P, Mortelmans L, de Hoon J, Bormans G. Gender-dependent increases with healthy aging of the human cerebral cannabinoid-type 1 receptor binding using [18F] MK-9470 PET. Neuroimage. 2008;39(4):1533-41.
33. Rodriguez JJ, Mackie K, Pickel VM. Ultrastructural localization of the CB1 cannabinoid receptor in {micro}-opioid receptor patches of the rat caudate putamen nucleus. J Neurosci. 2001;21(3):823-33.
34. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258(5090):1946-9.
35. Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K, Yamashita A, Waku K. 2-Arachidonoylgylcerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun. 1995;215(1):89-97.
36. Wilson RI, Nicoll RA. Endocannabinoid signaling in the brain. Science. 2002;296(5568):678-82.
37. Sugiura T, Kodaka T, Nakane S, Miyashita T, Kondo S, Suhara Y, Takayama H, Waku K, Seki C, Baba N. 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. 1999;274(5):2794-801.
38. Kishimoto Y, Kano M. Endogenous cannabinoid signaling through the CB1 receptor is essential for cerebellum-dependent discrete motor learning. J Neurosci. 2006;26(34):8829-37.
39. Hsieh C, Brown S, Derleth C, Mackie K. Internalization and recycling of the CB1 cannabinoid receptor. J Neurochem. 1999;73(2):493-501.
40. Rodriguez de Fonseca F, Gorriti MA, Fernandez-Ruiz JJ, Palomo T, Ramos JA. Downregulation of rat brain cannabinoid binding sites after chronic delta 9-tetrahydrocannabinol treatment. Pharmacol Biochem Behav. 1994;47(1):33-40.
41. Sim-Selley LJ, Schechter NS, Rorrer WK, Dalton GD, Hernandez J, Martin BR, Selley DE. Prolonged recovery rate of CB1 receptor adaptation after cessation of long-term cannabinoid administration. Mol Pharmacol. 2006;70(3):986-96.
42. Westlake TM, Howlett AC, Ali SF, Paule MG, Scallet AC, Slikker W Jr. Chronic exposure to delta 9-tetrahydrocannabinol fails to irreversibly alter brain cannabinoid receptors. Brain Res. 1991;544(1):145-9.
43. Sim LJ, Hampson RE, Deadwyler SA, Childers SR. Effects of chronic treatment with delta-9-tetrahydrocannabinol on cannabinoid-stimulated [35S]GTPgammaS autoradiography in rat brain. J Neurosci. 1996;16:8057-66.
44. Williams RW, Herrup K. The control of neuron number. Annu Rev Neurosci. 1988;11(1):423-53.
45. Dum RP, Strick PL. An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex. J Neurophysiol. 2003;89(1):634-9.
46. Middleton FA, Strick PL. Cerebellar output channels. Int Rev Neurobiol. 1997;41:61-82.
47. Middleton FA, Strick PL. Cerebellar projections to the prefrontal cortex of the primate. J Neurosci. 2001;21(2):700-12.
48. Schmahmann JD, Pandya DN. Anatomic organization of the basilar pontine projections from prefrontal cortices in rhesus monkey. J Neurosci. 1997;17(1):438-58.
49. Steinmetz JE. Brain substrates of classical eyeblink conditioning: a highly localized but also distributed system. Behav Brain Res. 2000;110(1-2):13-24.
50. Gerwig M, Hajjar K, Dimitrova A, Maschke M, Kolb FP, Frings M, Thilmann AF, Forsting M, Diener HC, Timmann D. Timing of conditioned eyeblink responses is impaired in cerebellar patients. J Neurosci. 2005;25(15):3919-31.
51. Heath RG, Dempesy CW, Fontana CJ, Fitzjarrell AT. Feedback loop between cerebellum and septal-hippocampal sites: its role in emotion and epilepsy. Biol Psychiatry. 1980;15(4):541-56.
52. Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain. 1998;121(4):561-79.
53. Corina DP, Jose-Robertson LS, Guillemin A, High J, Braun AR. Language lateralization in a bimanual language. J Cogn Neurosci. 2003;15(5): 718-30.
54. Roskies AL, Fiez JA, Balota DA, Raichle ME, Petersen SE. Task-dependent modulation of regions in the left inferior frontal cortex during semantic processing. J Cogn Neurosci. 2001;13(6):829-43.
55. Kanayama G, Rogowska J, Pope HG, Gruber SA, Yurgelun-Todd DA. Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study. Psychopharmacology (Berl). 2004;176(3): 239-47.
56. D'Souza DC, Abi-Saab WM, Madonick S, Forselius-Bielen K, Doersch A, Braley G, Gueorguieva R, Cooper TB, Krystal JH. Delta-9-tetra-hydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biol Psychiatry. 2005;57(6):594-608.
57. Green B, Kavanagh D, Young R. Being stoned: a review of self-reported cannabis effects. Drug Alcohol Rev. 2003;22(4):453-60.
58. Skosnik PD, Edwards CR, O'Donnell BF, Steffen A, Steinmetz JE, Hetrick WP. Cannabis use disrupts eyeblink conditioning: evidence for cannabinoid modulation of cerebellar-dependent learning. Neuropsychopharmacology. 2008;33(6):1432-40.
59. Pettit DAD, Harrison MP, Olson JM, Spencer RF, Cabral GA. Immuno-histochemical localization of the neural cannabinoid receptor in rat brain. J Neurosci Res. 1998;51(3):391-402.
60. Egertová M, Giang DK, Cravatt BF, Elphic MR. A new perspective on cannabinoid signalling: complimentary localization of fatty acid amide hydrolase and the CB1 receptor in rat brain. Proc Biol Sci. 1998;265(1410): 2081-5.
61. Tsou K, Nogueron MI, Muthian S, Sañudo-Peña MC, Hillard CJ, Deutsch DG, Walker JM. Fatty acid amide hydrolase is located preferentially in large neurons in the rat central nervous system as revealed by immuno-histochemistry. Neurosci Lett. 1998;254(3):137-40.
62. Tsou K, Brown S, Sañudo-Peña MC, Mackie K, Walker JM. Immunohis-tochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience. 1997;83(2):393-411.
63. Kreitzer AC, Regehr WG. Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron. 2001;29(3):717-27.
64. Howlett AC, Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, Porrino LJ. Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology. 2004;47:345-58.
65. Kreitzer AC, Regehr WG. Cerebellar depolarization-induced suppression of inhibition is mediated by endogenous cannabinoids. J Neurosci. 2001;21:1-5.
66. Safo PK, Regehr WG. Endocannabinoids control the induction of cerebel-lar LTD. Neuron. 2005;48(4):647-59.
67. Daniel H, Levenes C, Crépel F. Cellular mechanisms of cerebellar LTD. Trends Neurosci. 1998;21(9):401-7.
68. Napper RMA, Harvey RJ. Number of parallel fiber synapses on an individual Purkinje cell in the cerebellum of the rat. J Comp Neurol. 1988; 274(2):168-77.
69. Palay SL, Chan-Palay V. Cerebellar cortex. New York: Springer; 1974.
70. Rancz EA, Hausser M. Dendritic calcium spikes are tunable triggers of cannabinoid release and short-term synaptic plasticity in cerebellar Purkinje neurons. J Neurosci. 2006;26(20):5428-37.
71. Takahashi KA, Linden DJ. Cannabinoid receptor modulation of synapses received by cerebellar Purkinje cells. J Neurophysiol. 2000;83(3):1167-80.
72. Linden DJ. Neuroscience: from molecules to memory in the cerebellum. 2003:1682-5.
73. Ito M. Cerebellar long-term depression: characterization, signal transduction, and functional roles. Physiol Rev. 2001;81(3):1143-95.
74. Linden DJ, Dickinson MH, Smeyne M, Connor JA. A long-term depression of AMPA currents in cultured cerebellar Purkinje neurons. Neuron. 1991;7(1):81-9.
75. Coesmans M, Weber JT, De Zeeuw CI, Hansel C. Bidirectional parallel fiber plasticity in the cerebellum under climbing fiber control. Neuron. 2004;44(4):691-700.
76. Brenowitz SD, Regehr WG. Calcium dependence of retrograde inhibition by endocannabinoids at synapses onto Purkinje cells. J Neurosci. 2003; 23(15):6373-84.
77. Stella N, Schweitzer P, Piomelli D. A second endogenous cannabinoid that modulates long-term potentiation. Nature. 1997;388(6644):773-8.
78. Szabo B, Urbanski MJ, Bisogno T, Marzo VD, Mendiguren A, Baer WU, Freiman I. Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2-arachidonoylglycerol. J Physiol. 2006;577(1):263-80.
79. Brenowitz SD, Best AR, Regehr WG. Sustained elevation of dendritic calcium evokes widespread endocannabinoid release and suppression of synapses onto cerebellar Purkinje cells. J Neurosci. 2006;26(25):6841-50.
80. van Beugen BJ, Nagaraja RY, Hansel C. Climbing fiber-evoked endocannabinoid signaling heterosynaptically suppresses presynaptic cerebellar long-term potentiation. J Neurosci. 2006;26(32):8289-94.
81. Gormezano I, Kehoe EJ, Marshall BS. Twenty years of classical conditioning research with the rabbit. Prog Psychobiol Physiol Psychol. 1983; 10:197-275.
82. Christian KM, Thompson RF. Neural substrates of eyeblink conditioning: acquisition and retention. Learning Memory. 2003;10(6):427-55.
83. Gerwig M. The involvement of the human cerebellum in eyeblink conditioning. The Cerebellum. 2007;6(1):38-57.
84. Rogers RF, Britton GB, Steinmetz JE. Learning-related interpositus activity is conserved across species as studied during eyeblink conditioning in the rat. Brain Res. 2001;905(1-2):171-7.
85. Steinmetz JE. The cerebellum and classical eyeblink conditioning: much ado about something. In: Steinmetz JE, Gluck MA, Solomon PR, editors. Model systems and the neurobiology of associative learning: a festschrift in honor of Richard F. Thompson. Mahwah (NJ): Lawrence Erlbaum Associates; 2001. p. 217-44.
86. McCormick DA, Thompson RF. Neuronal responses of the rabbit cerebellum during acquisition and performance of a classically conditioned nictitating membrane-eyelid response. J Neurosci. 1984;4(11):2811-22.
87. Lavond DG, Steinmetz JE. Acquisition of classical conditioning without cerebellar cortex. Behav Brain Res. 1989;33(2):113-64.
88. Perrett SP, Ruiz BP, Mauk MD. Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses. J Neurosci. 1993; 13(4):1708-18.
89. Kleim JA, Freeman JH Jr, Bruneau R, Nolan BC, Cooper NR, Zook A, Walters D. Synapse formation is associated with memory storage in the cerebellum. Proc Natl Acad Sci U S A. 2002;99(20):13228-31.
90. Federmeier KD, Kleim JA, Greenough WT. Learning-induced multiple synapse formation in rat cerebellar cortex. Neurosci Lett. 2002;332(3): 180-4.
91. Mamounas LA, Thompson RF, Madden J. Cerebellar GABAergic processes: evidence for critical involvement in a form of simple associative learning in the rabbit. Proc Natl Acad Sci U S A. 1987;84(7):2101-5.
92. Bao S, Chen L, Kim JJ, Thompson RF. Cerebellar cortical inhibition and classical eyeblink conditioning. Proc Natl Acad Sci U S A. 2002;99(3): 1592-7.
93. Green JT, Steinmetz JE. Purkinje cell activity in the cerebellar anterior lobe after rabbit eyeblink conditioning. Learning Memory. 2005;12(3):260-9.
94. Ito M, Sakurai M, Tongroach P. Climbing fibre induced depression of both mossy fibre responsiveness and glutamate sensitivity of cerebellar Purkinje cells. J Physiol. 1982;324(1):113-34.
95. Kim JJ, Thompson RF. Cerebellar circuits and synaptic mechanisms involved in classical eyeblink conditioning. Trends Neurosci. 1997;20(4): 177-81.
96. Aiba A, Kano M, Chen C, Stanton ME, Fox GD, Herrup K, Zwingman TA, Tonegawa S. Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice. Cell. 1994;79(2):377-88.
97. Kishimoto Y, Kawahara S, Fujimichi R, Mori H, Mishina M, Kirino Y. Impairment of eyeblink conditioning in GluRd2-mutant mice depends on the temporal overlap between conditioned and unconditioned stimuli. Eur J Neurosci. 2001;14(9):1515-21.
98. Kishimoto Y, Kawahara S, Suzuki M, Mori H, Mishina M, Kirino Y. Classical eyeblink conditioning in glutamate receptor subunit 2 mutant mice is impaired in the delay paradigm but not in the trace paradigm. Eur J Neurosci. 2001;13(6):1249-53.
99. Shibuki K, Gomi H, Chen L, Bao S, Kim JJ, Wakatsuki H, Fujisaki T, Fujimoto K, Katoh A, Ikeda T. Deficient cerebellar long-term depression, impaired eyeblink conditioning, and normal motor coordination in GFAP mutant mice. Neuron. 1996;16(3):587-99.
100. Miyata M, Kim HT, Hashimoto K, Lee TK, Cho SY, Jiang H, Wu Y, Jun K, Wu D, Kano M. Deficient long-term synaptic depression in the rostral cerebellum correlated with impaired motor learning in phospholipase C beta4 mutant mice. Eur J Neurosci. 2001;13(10):1945-54.
101. Koekkoek SKE, Hulscher HC, Dortland BR, Hensbroek RA, Elgersma Y, Ruigrok TJH, De Zeeuw CI. Cerebellar LTD and learning-dependent timing of conditioned eyelid responses. Science. 2003;301(5640):1736-9.
102. Clark RE, Zhang AA, Lavond DG. Reversible lesions of the cerebellar interpositus nucleus during acquisition and retention of a classically conditioned behavior. Behav Neurosci. 1992;106(6):879-88.
103. Blaxton TA, Zeffiro TA, Gabrieli JDE, Bookheimer SY, Carrillo MC, Theodore WH, Disterhoft JF. Functional mapping of human learning: a positron emission tomography activation study of eyeblink conditioning. J Neurosci. 1996;16(12):4032-40.
104. Logan CG, Grafton ST. Functional anatomy of human eyeblink conditioning determined with regional cerebral glucose metabolism and positron-emission tomography. Proc Natl Acad Sci U S A. 1995;92(16): 7500-4.
105. Schreurs BG, McIntosh AR, Bahro M, Herscovitch P, Sunderland T, Molchan SE. Lateralization and behavioral correlation of changes in regional cerebral blood flow with classical conditioning of the human eyeblink response. J Neurophysiol. 1997;77(4):2153-63.
106. Edwards CR, Newman S, Bismark A, Skosnik PD, O'Donnell BF, Shekhar A, Steinmetz JE, Hetrick WP. Cerebellum volume and eyeblink conditioning in schizophrenia. Psychiatry Res. 2008;162(3):185-94. Epub 2008 Jan 28.
107. Woodruff-Pak DS, Vogel RW, Ewers M, Coffey J, Boyko OB, Lemieux SK. MRI-assessed volume of cerebellum correlates with associative learning. Neurobiol Learn Mem. 2001;76(3):342-57.
108. Ramnani N, Toni I, Josephs O, Ashburner J, Passingham RE. Learning-and expectation-related changes in the human brain during motor learning. J Neurophysiol. 2000;84(6):3026-35.
109. Knuttinen MG, Parrish TB, Weiss C, LaBar KS, Gitelman DR, Power JM, Mesulam MM, Disterhoft JF. Electromyography as a recording system for eyeblink conditioning with functional magnetic resonance imaging. Neuroimage. 2002;17(2):977-87.
110. Daum I, Schugens MM, Ackermann H, Lutzenberger W, Dichgans J, Birbaumer N. Classical conditioning after cerebellar lesions in humans. Behav Neurosci. 1993;107(5):748-56.
111. Woodruff-Pak DS, Papka M, Ivry RB. Cerebellar involvement in eyeblink classical conditioning in humans. Neuropsychology. 1996;10:443-58.
112. Ashton J, Appleton I, Darlington C, Smith P. Immunohistochemical localization of cannabinoid CB 1 receptor in inhibitory interneurons in the cerebellum. The Cerebellum. 2004;3(4):222-6.
113. Carter AG, Regehr WG. Prolonged synaptic currents and glutamate spillover at the parallel fiber to stellate cell synapse. J Neurosci. 2000; 20(12):4423-34.
114. Korbo L, Andersen BB, Ladefoged O, Moller A. Total numbers of various cell types in rat cerebellar cortex using an unbiased sterological method. Brain Res. 1993;609:262-8.
115. Brown SP, Brenowitz SD, Regehr WG. Brief presynaptic bursts evoke synapse-specific retrograde inhibition mediated by endogenous cannab-inoids. Nat Neurosci. 2003;6(10):1048-57.
116. Brenowitz SD, Regehr WG. Associative short-term synaptic plasticity mediated by endocannabinoids. Neuron. 2005;45(3):419-31.
117. Weiss C, Disterhoft JF. Eyeblink conditioning, motor control, and the analysis of limbic-cerebellar interactions. Behav Brain Sci. 1996;19:479-527.
118. Woodruff-Pak DS, Disterhoft JF. Where is the trace in trace conditioning? Trends Neurosci. 2008;31(2):105-12.
119. Edwards CR, Skosnik PD, Steinmetz A, Vollmer JM, O'Donnell BF, Hetrick WP. Assessment of forebrain-dependent trace eyeblink conditioning in chronic cannabis users. Neurosci Lett. 2008;439:264-8.
120. Clark RE, Squire LR. Classical conditioning and brain systems: the role of awareness. Science. 1998;280(5360):77-81.
121. Andreasson S, Allebeck P, Engstrom A, Rydberg U. Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet. 1987;2(8574): 1483-6.
122. Leweke FM, Giuffrida A, Wurster U, Emrich HM, Piomelli D. Elevated endogenous cannabinoids in schizophrenia. Neuroreport. 1999;10(8): 1665-9.
123. Moore THM, Zammit S, Lingford-Hughes A, Barnes TRE, Jones PB, Burke M, Lewis G. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. The Lancet. 2007;370(9584):319-28.
124. Ujike H, Takaki M, Nakata K, Tanaka Y, Takeda T, Kodama M, Fujiwara Y, Sakai A, Kuroda S. CNR1, central cannabinoid receptor gene, associated with susceptibility to hebephrenic schizophrenia. Mol Psychiatry. 2002; 7:515-8.
125. Giuffrida A, Leweke FM, Gerth CW, Schreiber D, Koethe D, Faulhaber J, Klosterkötter J, Piomelli D. Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology. 2004;29:2108-14.
126. Eggan SM, Hashimoto T, Lewis DA. Reduced cortical cannabinoid 1 receptor messenger RNA and protein expression in schizophrenia. Arch Gen Psychiatry. 2008;65(7):772-84.
127. Sears LL, Andreasen NC, O'Leary DS. Cerebellar functional abnormalities in schizophrenia are suggested by classical eyeblink conditioning. Biol Psychiatry. 2000;48(3):204-9.
128. Brown SM, Kieffaber PD, Carroll CA, Vohs JL, Tracy JA, Shekhar A, Steinmetz JE, Hetrick WP. Eyeblink conditioning deficits indicate timing and cerebellar abnormalities in schizophrenia. Brain Cogn. 2005;58(1): 94-108.
129. Marenco S, Weinberger DR, Schreurs BG. Single-cue delay and trace classical conditioning in schizophrenia. Biol Psychiatry. 2003;53(5):390-402.