Advertisement

Cerebellum and Eyeblink Conditioning

  • Derick H. Lindquist
  • Joseph E. Steinmetz
  • Richard F. Thompson

Abstract

The cerebellum and brainstem constitute the essential neural circuit responsible for the acquisition and expression of the classically conditioned eyeblink response in numerous mammalian species, including humans. In this simple form of motor learning, a neutral conditioned stimulus (CS) overlaps and coterminates with a mildly aversive unconditioned stimulus (US), resulting, eventually, in the production of an eyeblink conditioned response (CR) to the CS alone. The forebrain is engaged when this basic delay procedure is made more difficult – for instance, if the CS and US are separated by a brief stimulus-free gap of time. In either case, it is generally accepted that the critical memory trace is formed and stored in the cerebellar interpositus nucleus (IP). The cerebellar cortex also plays a key role in normal acquisition by modulating the amplitude and/or timing characteristics of the eyeblink CR. Owing to the well-defined nature of the neural circuit, and the close correspondence between animal and human studies, eyeblink conditioning has been successfully used to investigate cerebellar dysfunction across a variety of human populations. Herein, research related to three representative disorders is discussed: fetal alcohol syndrome, attention-deficit hyperactivity disorder, and schizophrenia. The results advance understanding of these and similar clinical pathologies and the cerebellar deficits that may underlie them.

Keywords

Purkinje Cell Unconditioned Stimulus Conditioned Response Fetal Alcohol Spectrum Disorder Fetal Alcohol Spectrum Disorder 
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.

References

  1. Anand B, Malhotra C, Singh B, Dua A (1959) Cerebellar projections to limbic system. J Neurophysiol 22(4):451–457PubMedGoogle Scholar
  2. Andreasen NC, Pierson R (2008) The role of the cerebellum in schizophrenia. Biol Psychiat 64:81–88PubMedCrossRefGoogle Scholar
  3. Andreasen NC, Paradiso S, O'Leary DS (1998) “Cognitive dysmetria” as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? Schizophrenia Bull 24(2):203–218CrossRefGoogle Scholar
  4. Bates E, Wilson SM, Saygin AP, Dick F, Sereno MI, Knight RT, Dronkers NF (2003) Voxel-based lesion-symptom mapping. Nat Neurosci 6:448–450PubMedGoogle Scholar
  5. Bayer SA, Altman J, Russo RJ, Zhang X (1993) Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. Neurotoxicology 14(1):83–144PubMedGoogle Scholar
  6. Bekinschtein TA, Shalom DE, Forcato C, Herrera M, Coleman MR, Manes FF, Sigman M (2009) Classical conditioning in the vegetative and minimally conscious state. Nat Neurosci 12(10):1343–1349PubMedCrossRefGoogle Scholar
  7. Berthier NE, Moore JW (1990) Activity of deep cerebellar nuclear cells during classical conditioning of nictitating membrane extension in rabbits. Exp Brain Res 83:44–54PubMedCrossRefGoogle Scholar
  8. Berthier NE, Desmond JE, Moore JW (1987) Brain stem control of the nictitating membrane response. In: Gormezano I, Prokasy WF, Thompson RF (eds) Classical conditioning. Lawrence Erlbaum, Mahwah, pp 275–286Google Scholar
  9. Bolbecker AR, Mehta C, Johannesen JK, Edwards CR, O'Donnell BF, Shekhar A, Nurnberger JI, Steinmetz JE, Hetrick WP (2009a) Eyeblink conditioning anomalies in bipolar disorder suggest cerebellar dysfunction. Bipolar Disord 11(1):19–32PubMedCrossRefGoogle Scholar
  10. Bolbecker AR, Mehta CS, Edwards CR, Steinmetz JE, O'Donnell BF, Hetrick WP (2009b) Eye-blink conditioning deficits indicate temporal processing abnormalities in schizophrenia. Schizophrenia Bull 111:182–191Google Scholar
  11. Britton GB, Astheimer LB (2004) Fear develops to the conditioned stimulus and to the context during classical eyeblink conditioning in rats. Integr Physiol Behav Sci 39(4):295–306PubMedCrossRefGoogle Scholar
  12. Brodal A, Walberg F, Hoddevik GH (1975) The olivocerebellar projection in the cat studied with the method of retrograde axonal transport of horseradish peroxidase. J Comp Neurol 164(4):449–469PubMedCrossRefGoogle Scholar
  13. Brown TH, Byrne JH, Labar K, LeDoux J, Lindquist DH, Thompson RF, Teyler TJ (2003) Learning and memory: basic mechanisms. In: Byrne JH, Roberts JL (eds) Cellular and molecular neuroscience. Academic, San Diego, pp 499–574Google Scholar
  14. Castellanos FX, Giedd JN, Marsh WL, Hamburger SD, Vaituzis AC, Dickstein DP, Sarfatti SE, Vauss YC, Snell JW, Lange N, Kaysen D, Krain AL, Ritchie GF, Rajapakse JC, Rapoport JL (1996) Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. Arch Gen Psychiatry 53(7):607–616PubMedCrossRefGoogle Scholar
  15. Castellanos FX, Giedd JN, Berquin PC, Walter JM, Sharp W, Tran T, Vaituzis AC, Blumenthal JD, Nelson J, Bastain TM, Zijdenbos A, Evans AC, Rapoport JL (2001) Quantitative brain magnetic resonance imaging in girls with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 58:289–295PubMedCrossRefGoogle Scholar
  16. Cegavske CF, Thompson RF, Patterson MM, Gormezano I (1976) Mechanisms of efferent neuronal control of the reflex nictitating membrane response in rabbit (Oryctolagus cuniculus). J Comp Physiol Psychol 90:411–423PubMedCrossRefGoogle Scholar
  17. Cegavske CF, Harrison TA, Torigoe Y (1987) Identification of the substrates of the unconditioned response in the classically conditioned, rabbit, nictitating-membrane preparation. In: Gormezano I, Prokasy WF, Thompson RF (eds) Classical conditioning. Lawrence Erlbaum, Mahwah, pp 65–93Google Scholar
  18. Chess AC, Green JT (2008) Abnormal topography and altered acquisition of conditioned eyeblink responses in a rodent model of attention-deficit/hyperactivity disorder. Behav Neurosci 122(1):63–74PubMedCrossRefGoogle Scholar
  19. Clark RE, Gohl EB, Lavond DG (1997) The learning-related activity that develops in the pontine nuclei during classical eye-blink conditioning is dependent on the interpositus nucleus. Learn Mem 3(6):532–544PubMedCrossRefGoogle Scholar
  20. Coffin JM, Roody S, Schneider K, O'Neill J (2005) Impaired cerebellar learning in children with prenatal alcohol exposure: a comparative study of eyeblink conditioning in children with ADHD and dyslexia. Cortex 41:389–398PubMedCrossRefGoogle Scholar
  21. Coleman SR, Gormezano I (1971) Classical conditioning of the rabbit’s (Oryctolagus cuniculus) nictitating membrane response under symmetrical CS-US interval shifts. J Comp Physiol Psychol 77(3):447–455PubMedCrossRefGoogle Scholar
  22. Dobbing J, Sands J (1979) The brain growth spurt in various mammalian species. Early Hum Dev 3:79–84PubMedCrossRefGoogle Scholar
  23. Edwards CR, Newman S, Bismark A, Skosnik PD, O'Donnell BF, Shekhar A, Steinmetz JE, Hetrick WP (2008) Cerebellum volume and eyeblink conditioning in schizophrenia. Psychiatry Res 162(3):185–194PubMedCrossRefGoogle Scholar
  24. Fanselow MS, Poulos AM (2005) The neuroscience of mammalian associative learning. Annu Rev Psychol 56:207–234PubMedCrossRefGoogle Scholar
  25. Freeman JH, Nicholson DA (2000) Developmental changes in eye-blink conditioning and neuronal activity in the cerebellar interpositus nucleus. J Neurosci 20(2):813–819PubMedGoogle Scholar
  26. Freeman JH, Nicholson DA (2001) Ontogenetic changes in the neural mechanisms of eyeblink conditioning. Integr Physiol Behav Sci 36(1):15–35PubMedCrossRefGoogle Scholar
  27. Frings M, Gaertner K, Buderath P, Gerwig M, Christiansen H, Schoch B, Gizewski ER, Hebebrand J, Timmann D (2010) Timing of conditioned eyeblink responses is impaired in children with attention-deficit/hyperactivity disorder. Exp Brain Res 201(2):167–176PubMedCrossRefGoogle Scholar
  28. Gerwig M, Dimitrova A, Kolb FP, Maschke M, Brol B, Kunnel A, Böring D, Thilmann AF, Forsting M, Diener HC, Timmann D (2003) Comparison of eyeblink conditioning in patients with superior and posterior inferior cerebellar lesions. Brain 126(Pt 1):71–94PubMedCrossRefGoogle Scholar
  29. Gerwig M, Kolb FP, Timmann D (2007) The involvement of the human cerebellum in eyeblink conditioning. Cerebellum 6:38–57PubMedCrossRefGoogle Scholar
  30. Gormezano I, Schneiderman N, Deauz E, Fuentes I (1962) Nictitating membrane: classical conditioning and extinction in the albino rabbit. Science 136:33–34CrossRefGoogle Scholar
  31. Gormezano I, Kehoe EJ, Marshall BS (1983) Twenty years of classical conditioning research with the rabbit. Prog Psychobiol Physiol Psychol 10:197–275Google Scholar
  32. Gould TJ, Steinmetz JE (1996) Changes in rabbit cerebellar cortical and interpositus nucleus activity during acquisition, extinction, and backward classical eyelid conditioning. Neurobiol Learn Mem 65:17–34PubMedCrossRefGoogle Scholar
  33. Green JT (2004) The effects of ethanol on the developing cerebellum and eyeblink classical conditioning. Cerebellum 3(3):178–187PubMedCrossRefGoogle Scholar
  34. Green JT, Steinmetz JE (2005) Purkinje cell activity in the cerebellar anterior lobe during rabbit eyeblink conditioning. Learn Mem 12(3):260–269PubMedCrossRefGoogle Scholar
  35. Green JT, Rogers RF, Goodlett CR, Steinmetz JE (2000) Impairment in eyeblink classical conditioning in adult rats exposed to ethanol as neonates. Alcohol Clin Exp Res 24(4):438–447PubMedCrossRefGoogle Scholar
  36. Green JT, Tran T, Steinmetz JE, Goodlett CR (2002) Neonatal ethanol produces cerebellar deep nuclear cell loss and correlated disruption of eyeblink conditioning in adult rats. Brain Res 956:302–311PubMedCrossRefGoogle Scholar
  37. Halverson HE, Freeman JH (2006) Medial auditory thalamic nuclei are necessary for eyeblink conditioning. Behav Neurosci 120:880–887PubMedCrossRefGoogle Scholar
  38. Halverson HE, Porembra A, Freeman JH (2008) Medial auditory thalamus inactivation prevents acquisition and retention of eyeblink conditioning. Learn Mem 15:532–538PubMedCrossRefGoogle Scholar
  39. Halverson HE, Lee I, Freeman JH (2010) Associative plasticity in the medial auditory thalamus and cerebellar interpositus nucleus during eyeblink conditioning. J Neurosci 30(26):8787–8796PubMedCrossRefGoogle Scholar
  40. Hill DE, Yeo RA, Campbell RA, Hart B, Vigil J, Brooks W (2003) Magnetic resonance imaging correlates of attention-deficit/hyperactivity disorder in children. Neuropsychol 17(3):496–506CrossRefGoogle Scholar
  41. Jacobson SW, Stanton ME, Molteno CD, Burden MJ, Fuller DS, Hoyme HE, Robinson LK, Khaole N, Jacobson JL (2008) Impaired eyeblink conditioning in children with fetal alcohol syndrome. Alcohol Clin Exp Res 32(2):365–372PubMedCrossRefGoogle Scholar
  42. Kalmbach BE, Ohyama T, Kreider JC, Riusech F, Mauk MD (2009) Interactions between prefrontal cortex and cerebellum revealed by trace eyelid conditioning. Learn Mem 16(1):86–95PubMedCrossRefGoogle Scholar
  43. Kalmbach BE, Ohyama T, Mauk MD (2010) Temporal patterns of inputs to cerebellum necessary and sufficient for trace eyelid conditioning. J Neurophysiol 104(2):627–640PubMedCrossRefGoogle Scholar
  44. Kleim JA, Freeman JH, Bruneau R, Nolan BC, Cooper NR, Zook A, Walters D (2002) Synapse formation is associated with memory storage in the cerebellum. Proc Natl Acad Sci 99(20):13228–13231PubMedCrossRefGoogle Scholar
  45. Kronforst-Collins MA, Disterhoft JF (1998) Lesions of the caudal area of rabbit medial prefrontal cortex impair trace eyeblink conditioning. Neurobiol Learn Mem 69:147–162PubMedCrossRefGoogle Scholar
  46. Krupa DJ, Thompson JK, Thompson RF (1993) Localization of a memory trace in the mammalian brain. Science 260:989–991PubMedCrossRefGoogle Scholar
  47. Lavond DG (2002) Role of the nuclei in eyeblink conditioning. Ann N Y Acad Sci 978:93–105PubMedCrossRefGoogle Scholar
  48. Lavond DG, Lincoln JS, McCormick DA, Thompson RF (1984) Effect of bilateral lesions of the dentate and interpositus cerebellar nuclei on conditioning of heart-rate and nictitating membrane/eyelid responses in the rabbit. Brain Res 305:323–330PubMedCrossRefGoogle Scholar
  49. Lavond DG, Logan CG, Sohn JH, Garner WD, Kanzawa SA (1990) Lesions of the cerebellar interpositus nucleus abolish both nictitating membrane and eyelid EMG conditioned responses. Brain Res 514(2):238–248PubMedCrossRefGoogle Scholar
  50. Lee T, Kim JJ (2004) Differential effects of cerebellar, amygdalar, and hippocampal lesions on classical eyeblink conditioning in rats. J Neurosci 24(13):3242–3250PubMedCrossRefGoogle Scholar
  51. Lindquist DH, Sokoloff G, Steinmetz JE (2007) Ethanol-exposed neonatal rats are impaired as adults in classical eyeblink conditioning at multiple unconditioned stimulus intensities. Brain Res 1150:155–166PubMedCrossRefGoogle Scholar
  52. Lindquist DH, Vogel RW, Steinmetz JE (2009) Associative and non-associative blinking in classically conditioned adult rats. Physiol Behav 96(3):399–411PubMedCrossRefGoogle Scholar
  53. Lindquist DH, Mahoney LP, Steinmetz JE (2010) Conditioned fear in adult rats is facilitated by the prior acquisition of a classically conditioned motor response. Neurobiol Learn Mem 94(2):167–175PubMedCrossRefGoogle Scholar
  54. Lubow RE (2009) Classical eyeblink conditioning and schizophrenia: a short review. Behav Brain Res 202:1–4PubMedCrossRefGoogle Scholar
  55. McCormick DA, Thompson RF (1984a) Cerebellum: essential involvement in the classically conditioned eyelid response. Science 223(4633):296–299PubMedCrossRefGoogle Scholar
  56. McCormick DA, Thompson RF (1984b) Neuronal responses of the rabbit cerebellum during acquisition and performance of a classically conditioned nictitating membrane-eyelid response. J Neurosci 4(11):2811–2822PubMedGoogle Scholar
  57. McCormick DA, Steinmetz JE, Thompson RF (1985) Lesions of the inferior olivary complex cause extinction of the classically conditioned eyelid response. Brain Res 359:120–130PubMedCrossRefGoogle Scholar
  58. McGlinchey-Berroth R, Cermak LS, Carrillo MC, Armfield S, Gabrieli JD, Disterhoft JF (1995) Impaired delay eyeblink conditioning in amnesic Korsakoff's patients and recovered alcoholics. Alcohol Clin Exp Res 19(5):1127–1132PubMedCrossRefGoogle Scholar
  59. McLaughlin J, Skaggs H, Churchwell J, Powell DA (2002) Medial prefrontal cortex and Pavlovian conditioning: trace versus delay conditioning. Behav Neurosci 116:37–47PubMedCrossRefGoogle Scholar
  60. Medina JF, Mauk MD (1999) Simulations of cerebellar motor learning: computational analysis of plasticity at the mossy fiber to deep nucleus synapse. J Neurosci 19(16):140–151Google Scholar
  61. Medina JF, Nores WL, Mauk MD (2002) Inhibition of climbing fibres is a signal for the extinction of conditioned eyelid responses. Nature 416(6878):330–333PubMedCrossRefGoogle Scholar
  62. Mintz M, Wang-Ninio Y (2001) Two stage theory of conditioning: Involvement of the cerebellum and the amygdala. Brain Res 897:150–156PubMedCrossRefGoogle Scholar
  63. Morara S, van der Want JJ, de Weerd H, Provini L, Rosina A (2001) Ultrastructural analysis of climbing fiber-Purkinje cell synaptogenesis in the rat cerebellum. Neuroscience 108:655–671PubMedCrossRefGoogle Scholar
  64. Neufeld M, Mintz M (2001) Involvement of the amygdala in classical conditioning of eyeblink response in the rat. Brain Res 889:112–117PubMedCrossRefGoogle Scholar
  65. Nolan BC, Freeman JH (2005) Purkinje cell Loss by OX7-saporin impairs excitatory and inhibitory eyeblink conditioning. Behav Neurosci 119:190–201PubMedCrossRefGoogle Scholar
  66. Oakley DA, Russell IS (1977) Subcortical storage of Pavlovian conditioning in the rabbit. Physiol Behav 18:931–937PubMedCrossRefGoogle Scholar
  67. Perrett SP, Ruiz BP, Mauk MD (1993) Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses. J Neurosci 13(4):1708–1718PubMedGoogle Scholar
  68. Pugh JR, Raman IM (2006) Potentiation of mossy fiber EPSCs in the cerebellar nuclei by NMDA receptor activation followed by postinhibitory rebound current. Neuron 51(1):113–123PubMedCrossRefGoogle Scholar
  69. Pugh JR, Raman IM (2008) Mechanisms of potentiation of mossy fiber EPSCs in the cerebellar nuclei by coincident synaptic excitation and inhibition. J Neurosci 28(42):10549–10560PubMedCrossRefGoogle Scholar
  70. Rogers RF, Britton GB, Steinmetz JE (2001) Learning-related interpositus activity is conserved across species as studies during eyeblink conditioning in the rat. Brain Res 905:171–177PubMedCrossRefGoogle Scholar
  71. Rorick-Kehn LM, Steinmetz JE (2005) Amygdalar unit activity during three learning tasks: eyeblink classical conditioning, Pavlovian fear conditioning, and signaled avoidance conditioning. Behav Neurosci 119(5):1254–1276PubMedCrossRefGoogle Scholar
  72. Rubia K, Noorloos J, Smith A, Gunning B, Sergeant J (2003) Motor timing deficits in community and clinical boys with hyperactive behavior: the effect of methylphenidate on motor timing. J Abnorm Child Psychol 31:301–313PubMedCrossRefGoogle Scholar
  73. Sagvolden T, Russell VA, Aase H, Johansen EB, Farshbaf M (2005) Rodent models of attention-deficit/hyperactivity disorder. Biol Psychiat 57:1239–1247PubMedCrossRefGoogle Scholar
  74. Schmahmann JD, Pandya DN (1995) Prefrontal cortex projections to the basilar pons in rhesus monkey: implications for the cerebellar contribution to higher function. Neurosci Lett 199(3):175–178PubMedCrossRefGoogle Scholar
  75. Sears LL, Steinmetz JE (1991) Dorsal accessory inferior olive activity diminishes during acquisition of the rabbit classically conditioned eyelid response. Brain Res 545:114–122PubMedCrossRefGoogle Scholar
  76. Sears LL, Finn PR, Steinmetz JE (1994) Abnormal classical eyeblink conditioning in autism. Autism Dev Disord 24:737–751CrossRefGoogle Scholar
  77. 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. Psychopharmacology 33(6):1432–1440Google Scholar
  78. Smith A, Taylor E, Rogers JW, Newman S, Rubia K (2002) Evidence for a pure time perception deficit in children with ADHD. J Child Psychol Psychiatry 43:529–542PubMedCrossRefGoogle Scholar
  79. Snider R, Maiti A, Snider S (1976) Cerebellar pathways to ventral midbrain and nigra. Exp Neurol 53(3):714–728PubMedCrossRefGoogle Scholar
  80. Sokol RJ, Delaney-Black V, Nordstrom B (2003) Fetal alcohol spectrum disorder. J Am Med Assoc 290:2996–2999CrossRefGoogle Scholar
  81. Stanton ME, Goodlett CR (1998) Neonatal ethanol exposure impairs eyeblink conditioning in weanling rats. Alcohol Clin Exp Res 22(1):270–275PubMedCrossRefGoogle Scholar
  82. Steinmetz JE (1990a) Classical nictitating membrane conditioning in rabbits with varying interstimulus intervals and direct activation of cerebellar mossy fibers as the CS. Behav Brain Res 38:97–108PubMedCrossRefGoogle Scholar
  83. Steinmetz JE (1990b) Neural activity in the cerebellar interpositus nucleus during classical NM conditioning with a pontine stimulation CS. Psychol Sci 1:378–382CrossRefGoogle Scholar
  84. Steinmetz JE (2000) Brain substrates of classical eyeblink conditioning: a highly localized but also distributed system. Behav Brain Res 110:13–24PubMedCrossRefGoogle Scholar
  85. Steinmetz JE, Lindquist DH (2009) Neuronal basis of learning. In: Berntson GG, Cacioppo JT (eds) Handbook of neuroscience for the behavioral sciences. Wiley, Hoboken, pp 507–527Google Scholar
  86. Steinmetz JE, Sengelaub DR (1992) Possible conditioned stimulus pathway for classical eyelid conditioning in rabbits. I. Anatomical evidence for direct projections from the pontine nuclei to the cerebellar interpositus nucleus. Behav Neural Biol 57:103–115PubMedCrossRefGoogle Scholar
  87. Steinmetz JE, Logan CG, Rosen DJ, Thompson JK, Lavond DG, Thompson RF (1987) Initial localization of the acoustic conditioned stimulus projection system to the cerebellum essential for classical eyelid conditioning. Proc Natl Acad Sci 84:3531–3535PubMedCrossRefGoogle Scholar
  88. Steinmetz JE, Lavond DG, Ivkovich D, Logan CG, Thompson RF (1992a) Disruption of classical eyelid conditioning after cerebellar lesions: damage to a memory trace system of a simple performance deficit? J Neurosci 12(11):4403–4426PubMedGoogle Scholar
  89. Steinmetz JE, Logue SF, Steinmetz SS (1992b) Rabbit classically conditioned eyelid responses do not reappear after interpositus nucleus lesion and extensive post-lesion training. Behav Brain Res 51:103–114PubMedCrossRefGoogle Scholar
  90. Taub AH, Mintz M (2010) Amygdala conditioning modulates sensory input to the cerebellum. Neurobiol Learn Mem 94(4):521–529PubMedCrossRefGoogle Scholar
  91. Thompson RF (1986) The neurobiology of learning and memory. Science 233:941–947PubMedCrossRefGoogle Scholar
  92. Thompson RF (2005) In search of memory traces. Ann Rev Psychol 56:1–23CrossRefGoogle Scholar
  93. Thompson RF, Krupa DJ (1994) Organization of memory traces in the mammalian brain. Ann Rev Neurosci 17:519–549PubMedCrossRefGoogle Scholar
  94. Thompson RF, Steinmetz JE (2009) The role of the cerebellum in classical conditioning of discrete behavioral responses. Neuroscience 162(3):732–755PubMedCrossRefGoogle Scholar
  95. Thompson RF, Donegan NH, Clark GA, Lavond DG, Lincoln JS, Madden J, Mamounas LA, Mauk MD, McCormick DA (1987) Neuronal substrates of discrete, defensive conditioned reflexes, conditioned fear states, and their interactions in the rabbit. In: Gormezano I, Prokasy WF, Thompson RF (eds) Classical conditioning, 3rd edn. Erlbaum, Hillsdale, pp 371–399Google Scholar
  96. Timmann D, Gerwig M, Frings M, Maschke M, Kolb FP (2005) Eyeblink conditioning in patients with hereditary ataxia: a one-year follow-up study. Exp Brain Res 162(3):332–345PubMedCrossRefGoogle Scholar
  97. Tracy JA, Ghose SS, Stetcher T, McFall RM, Steinmetz JE (1999) Classical conditioning in a nonclinical obsessive-compulsive population. Psychol Sci 10:9–13CrossRefGoogle Scholar
  98. Vogel RW, Amundson JC, Lindquist DH, Steinmetz JE (2009) Eyeblink conditioning during an interstimulus interval switch in rabbits (Oryctolagus cuniculus) using picrotoxin to disrupt cerebellar cortical input to the interpositus nucleus. Behav Neurosci 123(1):62–74PubMedCrossRefGoogle Scholar
  99. Wagner AR, Brandon SE (1989) Evolution of a structured connectionist model of Pavlovian conditioning (AESOP). In: Klein SB, Mowrer RR (eds) Contemporary learning theories: Pavlovian conditioning and the status of traditional learning theory. Erlbaum, Hillsdale, pp 149–190Google Scholar
  100. Weisz DJ, Harden DG, Xiang Z (1992) Effects of amygdala lesions on reflex facilitation and conditioned response acquisition during nictitating membrane response conditioning in rabbit. Behav Neurosci 106(2):262–273PubMedCrossRefGoogle Scholar
  101. Woodruff-Pak DS (2001) Eyeblink classical conditioning differentiates normal aging from Alzheimer’s disease. Integr Physiol Behav Sci 36(2):87–108PubMedCrossRefGoogle Scholar
  102. Woodruff-Pak DS, Disterhoft JF (2008) Where is the trace in trace conditioning? Trends in Neuroscience 31(2):105–112CrossRefGoogle Scholar
  103. Woodruff-Pak DS, Steinmetz JE (2000) Past, present, and future of human eyeblink classical conditioning. In: Woodruff-Pak DS, Steinmetz JE (eds) Eyeblink classical conditioning, vol 1, Applications in humans. Kluwer, Boston, pp 1–17Google Scholar
  104. Woodruff-Pak DS, Lavond DG, Logan CG, Steinmetz JE, Thompson RF (1993) Cerebellar cortical lesions and reacquisition in classical conditioning of the nictitating membrane response in rabbits. Brain Res 608:67–77PubMedCrossRefGoogle Scholar
  105. Yeo CH, Hardiman MJ, Glickstein M (1985) Classical conditioning of the nictitating membrane response of the rabbit: II. Lesions of the cerebellar cortex. Exp Brain Res 63:81–92Google Scholar
  106. Yeo CH, Hardiman MJ, Glickstein M (1986) Classical conditioning of nictitating membrane response of the rabbit: IV. Lesions of the inferior olive. Exp Brain Res 63:81–92PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Derick H. Lindquist
    • 1
  • Joseph E. Steinmetz
    • 3
  • Richard F. Thompson
    • 2
  1. 1.Department of PsychologyThe Ohio State UniversityColumbusUSA
  2. 2.Department of PsychologyUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.Department of PsychologyThe Ohio State UniversityColumbusUSA

Personalised recommendations