Conclusions
We have presented data addressing the relative contributions of the cerebellar cortex and nuclei in the acquisition and expression of conditioned eyelid responses. Data from a series of studies support the notion that while plasticity occurs in both the cerebellar cortex and nucleus, the cerebellar cortex is essential for acquisition, extinction, and for the proper expression of conditioned eyelid responses. We have presented arguments that the experiments that support this position were designed in ways to preclude confounds that were present in other attempts to identify the role of the cerebellar cortex in eyelid conditioning. We have also presented evidence that suggests plasticity in both the cerebellar cortex and nucleus is required for the expression of a conditioned response, and that reversing this plasticity only in the cerebellar cortex may be sufficient to produce extinction of conditioned responses. Computer simulations based on the connectivity of the cerebellum and on the sites and rules
for plasticity suggested by our studies are able to acquire properly timed conditioned responses, and to extinguish responses with CS-alone presentations. These simulations will provide many empirically testable predictions that should facilitate our understanding of the cerebellar mechanisms of eyelid conditioning.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
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 function. Mathematical Bioscience, 10, 25–61.
Bloedel, J.R. (1992). Functional heterogeneity with structural homogeneity: How does the cerebellum operate? Behavioral Neuroscience, 15, 666–678.
Bloedel. J.R., & Bracha, V. (1995). On the cerebellum, cutaneomuscular reflexes, movement control and the elusive engrams of memory. Behavioural Brain Research, 68, 1–44.
De Schutter, E. (1995). Cerebellar long-term depression might normalize excitation of Purkinje cells: A hypothesis. Trends in Neuroscience, 18, 291–295.
De Schutter E., & Maex, R. (1996). The cerebellum: cortical processing and theory. Current Opinions in Neurobiology, 6, 759–764.
Garcia, K.S., & Mauk, M.D. (1995). Cerebellar cortex is necessary for acquisition of Pavlovian eyelid responses. Society for Neuroscience Abstracts, 21, 1222.
Garcia, K.S., Mauk, M.D. (1998a). Pavlovian eyelid conditioning affects the amplitude and frequency of short-latency responses observed following pharmacological block of cerebellar cortex output. Society of Neuroscience Abstracts. 24, 444.
Garcia, K. S., & Mauk, M. D. (1998b). Pharmacological analysis of cerebellar contributions to the timing and expression of conditioned responses. Neuropharmacology, 37, 471–480.
Garcia, K.S., Stele, P.M., Mauk, M.D. (in press). Cerebellar cortex lesions prevent the acquisition of Pavlovian eyelid responses. Journal of Neuroscience.
Harvey, J.A., Welsh, J.P., Yeo, C.H., & Romano, A.G. (1993). Recoverable and nonrecoverable deficits in conditioned responses after cerebellar cortical lesions. Journal of Neuroscience, 13, 1624–1635.
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., & Ivarsson, M. (1994). Suppression of cerebellar Purkinje cells during conditioned responses in ferrets. Neuroreport, 5, 649–652.
Ito, M. (1982). Cerebellar control of the vestibulo-ocular reflex — around the flocculus hypothesis. Annual Review of Neuroscience, 5, 275–298.
Ito, M., & Kano, M. (1982a). Long-lasting depression of parallel fiber-Purkinje cell transmission induced by conjunctive stimulation of parallel fibers and climbing fibers in the cerebellar cortex. Neuroscience Letters, 33, 253–258.
Ito, M., Sakurai, M., & Tongroach, P. (1982b). Climbing fibre induced depression of both mossy fibre responsiveness and glutamate sensitivity of cerebellar Purkinje cells. Journal of Physiology (London), 324, 113–134.
Kenyon, G.T., Medina, J.F., & Mauk, M.D. (1998a). A mathematical model of the cerebellar-olivary system I: Self-regulating equilibrium of climbing fiber activity. Journal of Computational Neuroscience, 5, 17–33.
Kenyon, G.T., Medina, J.F., & Mauk, M.D. (1998b). A mathematical model of the cerebellar-olivary system II. Motor adaptation through systematic disruption of climbing fiber equilibrium. Journal of Computational Neuroscience, 5, 17–33.
Krupa, D.J., Thompson, J.K., & Thompson, R.F. (1993). Localization of a memory trace in the mammalian brain. Science, 260, 989–991.
Krupa, D.J., & Thompson, R.F. (1995). Inactivation of the superior cerebellar peduncle blocks expression but not acquisition of the rabbit’s classically conditioned eye-blink response. Proceedings of the National Academy of Sciences, (U.S.A), 92, 5097–5101.
Krupa, D.J., & Thompson, R.F. (1997). Reversible inactivation of the cerebellar interpositus nucleus completely prevents acquisition of the classicaly conditioned eye-blink response. Learning and Memory, 3, 545–556.
Lavond, D.G., & Steinmetz, J.E. (1989). Acquisition of classical conditioning without cerebellar cortex. Behavioural Brain Research, 33, 113–164.
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.
Lewis, J.L., LoTurco, J.J., & Solomon, P.R. (1987). Lesions of the middle cerebellar peduncle disrupt acquisition and retention of the rabbit’s classically conditioned nictitating membrane response. Behavioral Neuroscience, 101, 151–157.
Linden, D.J., & Connor, J.A. (1993). Cellular mechanisms of long-term depression in the cerebellum. Current Opinion in Neurobiology. 3, 401–6.
Linden, D.J., Dickinson, M.H., Smeyne, M., & Connor, J.A. (1991). A long-term depression of AMPA currents in cultured cerebellar Purkinje neurons. Neuron, 7, 81–9.
Lisberger, S.G. (1988). The neural basis for learning of simple motor skills. Science, 242, 728–35.
Lisberger, S.G., Pavelko, T.A., & Broussard, D.M. (1994). Neural basis for motor learning in the vestibuloocular reflex of primates. I. Changes in the responses of brain stem neurons. Journal of Neurophysiology, 72, 928–953.
Llinas, R., Lang, E.J., & Welsh, J.P. (1997). The cerebellum, LTD, and memory: alternative views. Learning and Memory, 3, 445–455.
Llinas, R., & Muhlethaler, M. (1988). An electrophysiological study of the in vitro, perfused brain stemcerebellum of adult guinea-pig. Journal of Physiology, (London), 404, 215–240.
Llinas, R., & Welsh, J.P. (1993). On the cerebellum and motor learning. Current Opinion in Neurobiology, 3, 958–965.
Marr, D. (1969). A theory of cerebellar cortex. Journal of Physiology, (London), 202, 437–70.
Mauk, M.D. (1997). Roles of cerebellar cortex and nuclei in motor learning: Contradictions of clues? Neuron, 18, 343–346.
Mauk, M.D. (1998). More than just another modifiable synapse. Neuron, 21, 649–651.
Mauk, M.D., & Donegan, N.H. (1997). A model of Pavlovian eyelid conditioning based on the synaptic organization of the cerebellum. Learning and Memory, 3, 130–158.
Mauk, M.D., Garcia, K.S., Medina, J.F., & Steele, P.M. (1998). Does cerebellar LTD mediate motor learning? Toward a resolution without a smoking gun. Neuron, 20, 359–362.
Mauk, M.D., & Ruiz, B.P. (1992). Learning-dependent timing of Pavlovian eyelid responses: differential conditioning using multiple interstimulus intervals. Behavioral Neuroscience, 106, 666–681.
Mauk, M.D., Steele, P.M., & Medina, J.F. (1997). Cerebellar involvement in motor learning. Neuroscientist, 3, 303–313.
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, (U.S.A.), 83, 5349–5353.
Matzel, L.D., & Shors, T.J. (1997). Long-term potentiation: What’s learning got to do with it? Behavioural Brain Sciences, 2, 0597–655.
McCormick, D.A., Clark, G.A., Lavond, D.G., & Thompson, R.F. (1982). Initial localization of the memory trace for a basic form of learning. Proceedings of the National Academy of Sciences, (U.S.A.), 79, 2731–2735.
McCormick, D.A., Steinmetz, J.E., & Thompson, R.F. (1985). Lesions of the inferior olivary complex cause extinction of the classically conditioned eyeblink response. Brain Research, 359, 120–130.
McCormick, D.A., & Thompson, R.F. (1984a). Cerebellum: essential involvement in the classically conditioned eyelid response. Science, 223, 296–299.
McCormick, D.A., & Thompson, R.F. (1984b). Neuronal responses of the rabbit cerebellum during acquisition and performance of a classically conditioned nictitating membrane-eyelid response. Journal of Neuroscience, 4, 2811–2822.
Miall, R.C., Keating, J.G., Malkmus, M., & Thach, W.T. (1998). Simple spike activity predicts occurrence of complex spikes in cerebellar Purkinje cells. Nature Neuroscience, I, 13–15.
Miles, F.A., & Lisberger, S.G. (1981). Plasticity in the vestibulo-ocular reflex: A new hypothesis. Annual Review of Neuroscience, 4, 273–299.
Millenson, J.R., Kehoe, E.J., & Gormezano, I. (1977). Classical conditioning of the rabbit’s nictitating membrane response under fixed and mixed CS-US intervals. Learning and Motivation, 8, 351–366.
Perrett, S.P., & Mauk, M.D. (1995). Extinction of conditioned eyelid responses requires the anterior lobe of cerebellar cortex. Journal of Neuroscience, 15, 2074–2080.
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.
Raymond, J.L., & Lisberger, S.G. (1998). Neural learning rules for the vestibulo-ocular reflex. Journal of Neuroscience, 18, 9112–9129.
Raymond, J.L., Lisberger, S.G., & Mauk, M.D. (1996). The cerebellum: a neuronal learning machine? Science, 272, 1126–1131.
Sakurai, M. (1987). Synaptic modification of parallel fibre-Purkinje cell transmission in in vitro guinea-pig cerebellar slices. Journal of Physiology, (London), 394, 463–480.
Salin, P.A., Malenka, R.C., & Nicoll, R.A. (1996). Cyclic AMP mediates a presynaptic form of LTP at cerebellar parallel fiber synapses. Neuron, 16, 797–803.
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.
Stele, P.M., Medina, J.F., Nores, W.L., & Mauk, M.D. (1998). Using genetic mutations to study the neural basis of behavior. Cell, 95, 879–882.
Steele, P.M., Nores, W.L., Medina, J.F., & Mauk, M.D. (1999). Induction of plasticity in the interpositus nucleus during eyelid conditioning requires input from the cerebellar cortex. Cold Spring Harbor Abstracts.
Steinmetz, J.E. (1990). Classical nictitating membrane conditioning in rabbits with varying interstimulus intervals and direct activation of cerebellar mossy fibers as the CS. Behavioural Brain Research, 38, 97–108.
Steinrnetz, 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, (U.S.A.), 84, 3531–3535.
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.
Tracy, J.A., Thompson, J.K., Krupa, D.J., & Thompson, R.F. (1998). Evidence of plasticity in the pontocerebellar conditioned stimulus pathway during classical conditioning of the eyeblink response in the rabbit. Behavioral Neuroscience, 112, 267–285.
Welsh, J.P., & Harvey, J.A. (1991). Pavlovian conditioning in the rabbit during inactivation of the interpositus nucleus. Journal of Physiology, (London), 444, 459–480.
Woodruff-Pak, D.S., Lavond, D.G., Logan, C.G., Steinmetz, J.E., & Thompson, R.F. (1993). Cerebellar cortical lesions and reacquisition in classical conditioning of the nictitating membrane response in rabbits. Brain Research, 608, 67–77.
Yeo, C.H., & Hardiman, M.J. (1992). Cerebellar cortex and eyeblink conditioning: a reexamination. Experimental Brain Research, 88, 623–638.
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. (1985). Classical conditioning of the nictitating membrane response of the rabbit. III. Connections of cerebellar lobule HVI. Experimental Brain Research, 60, 114–126.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Kluwer Academic Publishers
About this chapter
Cite this chapter
Nores, W.L., Medina, J.F., Steele, P.M., Mauk, M.D. (2002). Relative Contributions of the Cerebellar Cortex and Cerebellar Nucleus to Eyelid Conditioning. In: Woodruff-Pak, D.S., Steinmetz, J.E. (eds) Eyeblink Classical Conditioning: Volume 2. Springer, Boston, MA. https://doi.org/10.1007/0-306-46897-2_9
Download citation
DOI: https://doi.org/10.1007/0-306-46897-2_9
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-7923-7863-1
Online ISBN: 978-0-306-46897-1
eBook Packages: Springer Book Archive