NEUROSCIENCE AND LEARNING: LESSONS FROM STUDYING THE INVOLVEMENT OF A REGION OF CEREBELLAR CORTEX IN EYEBLINK CLASSICAL CONDITIONING
Corresponding Author
Joseph E. Steinmetz Ph.D.
INDIANA UNIVERSITY
Department of Psychology, Indiana University, 1101 E. 10th Street, Bloomington, Indiana 47405-7007, Telephone: 812-855-6414, Fax: 812-855-4691 (e-mail: [email protected]).Search for more papers by this authorCorresponding Author
Joseph E. Steinmetz Ph.D.
INDIANA UNIVERSITY
Department of Psychology, Indiana University, 1101 E. 10th Street, Bloomington, Indiana 47405-7007, Telephone: 812-855-6414, Fax: 812-855-4691 (e-mail: [email protected]).Search for more papers by this authorAbstract
How the nervous system encodes learning and memory processes has interested researchers for 100 years. Over this span of time, a number of basic neuroscience methods has been developed to explore the relationship between learning and the brain, including brain lesion, stimulation, pharmacology, anatomy, imaging, and recording techniques. In this paper, we summarize how different research approaches can be employed to generate converging data that speak to how structures and systems in the brain are involved in simple associative learning. To accomplish this, we review data regarding the involvement of a particular region of cerebellar cortex (Larsell's lobule HVI) in the widely used paradigm of classical eyeblink conditioning. We also present new data on the role of lobule HVI in eyeblink conditioning generated by combining temporary brain inactivation and single-cell recording methods, an approach that looks promising for further advancing our understanding of relationships between brain and behavior.
REFERENCES
- Aizenman, C. D., Manis, P. B., & Linden, D. J. (1998). Polarity of long-term synaptic gain change is related to postsynaptic spike firing at a cerebellar inhibitory synapse. Neuron, 21, 827–835.
-
Albus, J. S. (1971). A theory of cerebellar functions.
Mathematical Biosciences, 10, 25–61.
10.1016/0025-5564(71)90051-4 Google Scholar
- Andersson, G., & Hesslow, G. (1987). Activity of Purkinje cells and interpositus neurons during and after periods of high frequency climbing fibre activation in the cat. Experimental Brain Research, 67, 533–542.
- Attwell, P. J., Cooke, S. F., & Yeo, C. H. (2002). Cerebellar function in consolidation of a motor memory. Neuron, 34(6), 1011–20.
- Attwell, P. J., Rahman, S., Ivarsson, M., & Yeo, C. H. (1999). Cerebellar cortical AMPA-kainate receptor blockade prevents performance of classically conditioned nictitating membrane responses. Journal of Neuroscience, 19, RC45.
- Attwell, P. J., Rahman, S., & Yeo, C. H. (2001). Acquisition of eyeblink conditioning is critically dependent on normal function in cerebellar cortical lobule HVI. Journal of Neuroscience, 21, 5715–5722.
- Baker, K. B., Tracy, J., Villarreal, R. P., & Steinmetz, J. E. (2002 November). Inactivation of interpositus nucleus of cerebellum during eyeblink conditioning causes conditioned response (CR) impairment but not loss of learning-related activity in HVI region of cerebellar cortex. Poster presented at the Society for Neuroscience Meeting, Orlando, Florida.
- Berger, T. W., & Thompson, R. F. (1978). Neuronal plasticity in the limbic system during classical conditioning of the rabbit nictitating membrane response. I. The hippocampus. Brain Research, 145, 323–346.
- Berthier, N. E., & Moore, J. W. (1986). Cerebellar Purkinje cell activity related to the classically conditioned nictitating membrane response. Experimental Brain Research, 63, 341–350.
- Brodal, A. (1940). The cerebellum of the rabbit. Journal of Comparative Neurology, 72, 63–81.
- Brodal, A., & Jansen, J. (1946). The ponto-cerebellar projection in the rabbit and cat. Journal of Comparative Neurology, 84, 31–118.
- Chen, L., Bao, S., Lockard, J. M., Kim, J. J., & Thompson, R. F. (1996). Impaired classical eyeblink conditioning in cerebellar lesioned and Purkinje cell degeneration (pcd) mutant mice. Journal of Neuroscience, 16, 2829–2838.
- Clark, R. E., & Lavond, D. G. (1996). Neural unit activity in the trigeminal complex with interpositus or red nucleus inactivation during classical eyeblink conditioning. Behavioral Neuroscience, 110, 1–9.
- Clark, R. E., Zhang, A. A., & Lavond, D. G. (1992). Reversible lesions of the cerebellar interpositus nucleus during acquisition and retention of a classically conditioned behavior. Behavioral Neuroscience, 106, 879–888.
- Ekerot, C. F., & Kano, M. (1985). Long-term depression of parallel fibre synapses following stimulation of climbing fibres. Brain Research, 342, 357–360.
- Fanselow, M. S. (2001). Toward a neurobiology of functional behavior systems: Contrasting Pavlovian emotional and motor learning. In J. E. Steinmetz, M. A. Gluck, & P. R. Solomon (Eds.), Model systems and the neurobiology of associative learning: A festschrift in honor of Richard F. Thompson (pp. 379–393). Mahwah, NJ: Erlbaum.
- Garcia, K. S., Mauk, M. D., Weidemann, G., & Kehoe, E. J. (2003). Covariation of alternative measures of responding in rabbit (Oryctalagus cuniculus) eyeblink conditioning during acquisition training and tone generalization. Behavioral Neuroscience, 117, 292–303.
- Gormezano, I. (1966). Classical conditioning. In J. B. Sidowski (Ed.), Experiment methods and instrumentation in psychology (pp. 385–420). New York: McGraw-Hill.
- Gormezano, I., Kehoe, E. J., & Marshall, B. S. (1983). Twenty years of classical conditioning with the rabbit. Progress in Psychobiology and Physiological Psychology, 10, 197–275.
- Gould, T. J., & Steinmetz, J. E. (1996). Changes in rabbit cerebellar cortical and interpositus nucleus activity during acquisition, extinction, and backward classical eyelid conditioning. Neurobiology of Learning & Memory, 65, 17–34.
- Hesslow, G. (1994). Inhibition of classically conditioned eyeblink responses by stimulation of the cerebellar cortex in the decerebrate cat. Journal of Physiology (London), 476, 245–256.
- Hesslow, G., Svensson, P., & Ivarsson, M. (1999). Learned movements elicited by direct stimulation of cerebellar mossy fiber afferents. Neuron, 24, 179–185.
- Hirano, T. (1990). Depression and potentiation of the synaptic transmission between a granule cell and a Purkinje cell in rat cerebellar culture. Neuroscience Letters, 119, 141–144.
- Ito, M. (1989). Long-term depression. Annual Review Of Neuroscience, 12, 85–102.
- Jahnsen, H. (1986). Electrophysiological characteristics of neurons in the guinea-pig deep cerebellar nuclei in vitro. Journal of Physiology (London), 372, 129–147.
- Jorntell, H., & Ekerot, C.-F. (2002). Reciprocal bidirectional plasticity of parallel fiber receptive fields in cerebellar Purkinje cells and their afferent interneurons. Neuron, 34, 797–806.
- Katz, D. B., & Steinmetz, J. E. (1997). Single-unit evidence for eye-blink conditioning in cerebellar cortex is altered, but not eliminated, by interpositus nucleus lesions. Learning & Memory, 4, 88–104.
- Katz, D. B., Tracy, J. A., & Steinmetz, J. E. (2001). Rabbit classical eyeblink conditioning is altered by brief cerebellar cortical stimulation. Physiology & Behavior, 72, 499–510.
- Krupa, D. J., Thompson, J. K., & Thompson, R. F. (1993, May 14). Localization of a memory trace in the mammalian brain. Science, 260, 898–991.
- Lavond, D. G., & Kanzawa, S. A. (2001). Inside the black box. In J. E. Steinmetz, M. A. Gluck, & P. R. Solomon (Eds.), Model systems and the neurobiology of associative learning: A festschrift in honor of Richard F. Thompson (pp. 245–269). Mahwah, NJ: Erlbaum.
-
Lavond, D. G., &
Steinmetz, J. E. (2003). Handbook of classical conditioning. Boston: Kluwer.
10.1007/978-1-4615-0263-0 Google Scholar
- Lavond, D. G., Steinmetz, J. E., Yokaitis, M. H., & Thompson, R. F. (1987). Reacquisition of classical conditioning after removal of cerebellar cortex. Experimental Brain Research, 67, 569–593.
- Linden, D. J., & Conner, J. A. (1991, December 13). Participation of postsynaptic PKC in cerebellar long-term depression in culture. Science, 254, 1656–1659.
- Lisberger, S. G., Pavelko, T. A., Bronte-Stewart, H. M., & Stone, L. S. (1994). Neural basis for motor learning in the vestibuloocular reflex of primates. II. Changes in the responses of horizontal gaze velocity Purkinje cells in the cerebellar flocculus and ventral paraflocculus. Journal of Neurophysiology, 72, 954–973.
- Marr, D. (1969). A theory of cerebellar cortex. Journal of Physiology, 202, 437–470.
- Mauk, M. D., & Donegan, N. H. (1997). A model of Pavlovian eyelid conditioning based on the synaptic organization of the cerebellum. Learning & Memory, 3, 130–158.
- Mauk, M. D., & Thompson, R. F. (1987). Retention of classically conditioned eyelid responses following acute decerebration. Brain Research, 403, 89–95.
- Mauk, M. D., Steinmetz, J. E., & Thompson, R. F. (1986). Classical conditioning using stimulation of the inferior olive as the unconditioned stimulus. Proceedings of the National Academy of Sciences (USA), 83, 5349–5353.
- McCormick, D. A., Lavond, D. G., & Thompson, R. F. (1982). Concomitant classical conditioning of the rabbit nictitating membrane and eyelid responses: Correlations and implications. Physiology and Behavior, 28, 769–775.
- McCormick, D. A., & Thompson, R. F. (1984, January 20). Cerebellum: Essential involvement in the classically conditioned eyelid response. Science, 223, 296–299.
- McCrea, R. A., Bishop, G. A., & Kitai, S. T. (1977). Electrophysiological and horseradish peroxidase studies of precerebellar afferents to the nucleus interpositus anterior: II. Mossy fiber system. Brain Research, 122, 215–228.
- Medina, J. F., & Mauk, M. D. (1999). Simulations of cerebellar motor learning: Computational analysis of plasticity at the mossy fiber to deep nucleus synapse. Journal of Neuroscience, 19, 7140–7151.
- Medina, J. F., Nores, W. L., Ohyama, T., & Mauk, M. D. (2000). Mechanisms of cerebellar learning suggested by eyelid conditioning. Current Opinion in Neurobiology, 10, 717–724.
- J. W. Moore (Ed.). (2002), A neuroscientist's guide to classical conditioning. New York: Springer.
- Moyer, J. R., Jr., Deyo, R. A., & Disterhoft, J. F. (1990). Hippocampectomy disrupts trace eye-blink conditioning in rabbits. Behavioral Neuroscience, 104, 243–252.
- Oakley, D. A., & Russell, I. S. (1972). Neocortical lesions and Pavlovian conditioning. Physiology & Behavior, 8, 915–926.
- Olds, J., Disterhoft, J. F., Segal, M., Kornblith, C. L., & Hirsh, R. (1972). Learning centers of the rat brain mapped by measuring latencies of conditioned unit responses. Journal of Neurophysiology, 35, 202–219.
-
Pavlov, I. P. (1927). Conditioned reflexes. Oxford: Oxford University Press.
10.3109/00016482709120085 Google Scholar
- Perrett, S. P., Ruiz, B. P., & Mauk, M. D. (1993). Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses. Journal of Neuroscience, 13, 1708–1718.
- Schmaltz, L. W., & Theios, J. (1972). Acquisition and extinction of a classically conditioned response in hippocampectomized rabbits (Oryctolagus cuniculus). Journal of Comparative & Physiological Psychology, 79, 328–333.
- Schreurs, B. G., & Alkon, D. L. (1993). Rabbit cerebellar slice analysis of long-term depression and its role in classical conditioning. Brain Research, 631, 235–240.
- Schreurs, B. G., Sanchez-Andres, J. V., & Alkon, D. L. (1991). Learning-specific differences in Purkinje-cell dendrites of lobule HVI (Lobulus simplex): Intracellular recording in a rabbit cerebellar slice. Brain Research, 548, 18–22.
- Sears, L. L., & Steinmetz, J. E. (1990). Acquisition of classically conditioned-related activity in the hippocampus is affected by lesions of the cerebellar interpositus nucleus. Behavioral Neuroscience, 104, 681–692.
- Shinkman, P. G., Swain, R. A., & Thompson, R. F. (1996). Classical conditioning with electrical stimulation of cerebellum as both conditioned and unconditioned stimulus. Behavioral Neuroscience, 110, 914–921.
- Skelton, R. W. (1988). Bilateral cerebellar lesions disrupt conditioned eyelid responses in unrestrained rats. Behavioral Neuroscience, 102, 586–590.
- Solomon, P. R., Schaaf, Vander E. R., Thompson, R. F., & Weisz, D. J. (1986). Hippocampus and trace conditioning of the rabbit's classically conditioned nictitating membrane response. Behavioral Neuroscience, 100, 729–744.
- Stanton, M. E., Freeman, J. H., Jr., & Skelton, R. W. (1992). Eyeblink conditioning in the developing rat. Behavioral Neuroscience, 106, 657–665.
- Steinmetz, J. E. (2000). Brain substrates of classical eyeblink conditioning: A highly localized but also distributed system. Behavioural Brain Research, 110, 13–24.
- Steinmetz, J. E., Kim, J., & Thompson, R. F. (2002). Biological models of associative learning. In M. Gallagher & R. Nelson (Eds.), Handbook of psychology: Vol. 3. Biological psychology (pp. 499–541). New York: Wiley.
- Steinmetz, J. E., Lavond, D. G., & Thompson, R. F. (1989). Classical conditioning in rabbits using pontine nucleus stimulation as a conditioned stimulus and inferior olive stimulation as an unconditioned stimulus. Synapse, 3, 225–233.
- Steinmetz, J. E., Logan, C. G., Rosen, D. J., Thompson, J. K., Lavond, D. G., & Thompson, R. F. (1987). Initial localization of the acoustic conditioned stimulus projection system to the cerebellum essential for classical eyelid conditioning. Proceedings of the National Academy of Sciences (USA), 84, 3531–3535.
- Steinmetz, J. E., Logue, S. F., & Steinmetz, S. S. (1992). Rabbit classically conditioned eyelid responses do not reappear after interpositus nucleus lesion and extensive post-lesion training. Behavioural Brain Research, 51, 103–114.
- Steinmetz, J. E., Rosen, D. J., Chapman, P. F., Lavond, D. G., & Thompson, R. F. (1986). Classical conditioning of the rabbit eyelid response with a mossy-fiber stimulation CS: I. Pontine nuclei and middle cerebellar peduncle stimulation. Behavioral Neuroscience, 100, 878–887.
- Steinmetz, J. E., & Sengelaub, D. R. (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. Behavioral & Neural Biology, 57, 103–115.
- Swain, R. A., Shinkman, P. G., Nordholm, A. F., & Thompson, R. F. (1992). Cerebellar stimulation as an unconditioned stimulus in classical conditioning. Behavioral Neuroscience, 106, 739–750.
- Swain, R. A., Shinkman, P. G., Thompson, J. K., Grethe, J. S., & Thompson, R. F. (1999). Essential neuronal pathways for reflex and conditioned response initiation in an intracerebellar stimulation paradigm and the impact of unconditioned stimulus preexposure on learning rate. Neurobiology of Learning & Memory, 71, 167–193.
- Yeo, C. H., Hardiman, M. J., & Glickstein, M. (1984). Discrete lesions of the cerebellar cortex abolish the classically conditioned nictitating membrane response of the rabbit. Behavioural Brain Research, 13, 261–266.
- Yeo, C. H., Hardiman, M. J., & Glickstein, M. (1985a). Classical conditioning of the nictitating membrane response of the rabbit. II. Lesions of the cerebellar cortex. Experimental Brain Research, 60, 99–113.
- Yeo, C. H., Hardiman, M. J., & Glickstein, M. (1985b). Classical conditioning of the nictitating membrane response of the rabbit. III. Connections of cerebellar lobule HVI. Experimental Brain Research, 60, 114–126.
- Young, R. A., Cegavske, C. F., & Thompson, R. F. (1976). Tone-induced changes in excitability of abducens motoneurons and of the reflex path of nictitating membrane response in rabbit (Oryctolagus cuniculus). Journal of Comparative and Physiological Psychology, 90, 424–434.
- Zhang, J., Ni, H., & Harper, R. M. (1986). A miniaturized cryoprobe for functional neuronal blockade in freely-moving animals. Journal of Neuroscience, 16, 79–87.