Abstract
Previous studies using rabbits and ferrets found that electrical stimulation of the pontine nuclei or middle cerebellar peduncle could serve as a conditioned stimulus (CS) in eyeblink conditioning (Bao, Chen, & Thompson, 2000; Hesslow, Svensson, & Ivarsson, 1999; Steinmetz, 1990; Steinmetz, Lavond, & Thompson, 1985; 1989; Steinmetz et al., 1986; Tracy, Thompson, Krupa, & Thompson, 1998). The current study used electrical stimulation of the pontine nuclei as a CS to establish eyeblink conditioning in rats. The goals of this study were to develop a method for directly activating the CS pathway in rodents and to compare the neural circuity underlying eyeblink conditioning in different mammalian species. Rats were given electrical stimulation through a bipolar electrode implanted in the pontine nuclei paired with a periorbital shock unconditioned stimulus (US). Paired training was followed by extinction training. A subset of rats was given a test session of paired training after receiving an infusion of muscimol into the anterior interpositus nucleus. Rats given paired presentations of the stimulation CS and US developed CRs rapidly and showed extinction. Muscimol infusion prior to the test session resulted in a reversible loss of the eyeblink CR. The results demonstrate that electrical stimulation of the pontine nuclei can be used as a CS in rodents and that the CS pathway is similar in rats, rabbits, and ferrets. In addition, the loss of CRs following muscimol inactivation shows that the conditioning produced with pontine stimulation depends on cerebellar mechanisms.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bao S., Chen, L., & Thompson, R.F. (2000). Learning- and cerebellum-dependent neuronal activity in the leteral pontine nucleus.Behavioral Neuroscience, 114, 254–261.
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.
Berthier, N.E., & Moore, J.W. (1990). Activity of deep cerebellar nuclear cells during classical conditioning of nictitating membrane extension in rabbits.Experimental Brain Research, 83, 44–54.
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.
Chen, L., Bao, S., & Thompson, R.F. (1999). Bilateral lesions of the interpositus nucleus completely prevent eyeblink conditioning in Purkinje cell-degeneration mutant mice.Behavioral Neuroscience, 113, 204–210.
Christian, K.M., & Thompson, R.F. (2003). Neural, substrates of eyeblink conditioning: acquisition and retention.Learning & Memory, 10, 427–455.
Clark, R.E., Gohl, E.B., & Lavond, D.G. (1997). The learning-related activity, that develops in the pontine nuclei during classical eye-blink conditioning is dependent on the interpositus nucleus.Learning and Memory, 3, 532–544.
Daum, I., Schugens, M.M., Ackermann, H., Lutzenberger, W., Dichgans, J., & Birbaumer, N. (1993). Classical conditioning after cerebellar lesions in humans.Behavioral Neuroscience, 107, 748–756.
Freeman, J.H., Jr., Carter, C.S., & Stanton, M.E. (1995). Early cerebellar lesions impair eyeblink conditioning in developing rats: differential effects of unilateral lesions on postnatal day 10 or 20.Behavioral Neuroscience, 109, 893–902.
Freeman, J.H., Jr., & Muckler, A.S., (2003). Developmental changes in eyeblink conditioning and neuronal activity in the pontine nuclei.Learning & Memory, 10, 337–345.
Freeman, J.H., Jr., & Nicholson, D.A. (1999). Neuronal activity in the cerebellar interpositus and lateral pontine nuclei during inhibitory classical conditioning of the eyeblink response.Brain Research, 833, 225–233.
Freeman, J.H., Jr., & Nicholson, D.A. (2004). Developmental changes in the neural mechanisms of eyeblink conditioning.Behavioral and Cognitive Neuroscience Reviews, 3, 3–13.
Gormezano, I., Kehoe, E.J., & Marshall, B.S. (1983). Twenty years of classical conditioning research 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 and Memory, 65, 17–34.
Green, J.T., Rogers, R.F., Goodlett, C.R., & Steinmetz, J.E. (2000). Impariment in eyeblink classical conditioning in adult rats exposed to ethanol as neonates.Alcoholism: Clinical & Experimental Research, 24, 438–447.
Green, J.T., Johnson, T.B., Goodlett, C.R, & Steinmetz, J.E. (2002). Eyblink classical conditioning and interpositus nucleus activity are disrupted in adult are disrupted in adult rats exposed to ethanol as neonates.Learning & Memory, 9, 304–320.
Hesslow, G., Svensson, P., & Ivarsson, M. (1999). Learned movements elicited by direct stimulation of cerebellar mossy fiber afferents.Neuron, 24, 179–185.
Kehoe, E.J., & Napier, R.M. (1991). Temporal specificity in cross-modal transfer of the rabbit nictitating membrane response.Journal of Experimental Psychology: Animal Behavior Processes, 17, 26–35.
Kim, J.J., Krupa, D.J., & Thompson, R.F. (1998). Inhibitory cerebello-olivary projections and blocking effect in classical conditioning.Science, 279, 570–573.
Lee, T., & Kim, J.J. (2004). Differential effects of cerebellar, amygdalar, and hippocampal lesions on classical eyeblink conditioning in rats.Journal of Neuroscience, 24, 3242–3250.
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 83, 5349–5353.
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, 79, 2731–2735.
McCormick, D.A., Lavond, D.G., & Thompson, R.F. (1983). Neuronal responses of the rabbit brainstem during performance of the classically conditioned nictitating membrane (NM)/eyelid response.Brain Research, 271, 73–88.
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, 11, 2811–2822.
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.
Mihailoff, G.A. (1993). Cerebellar nuclear projections from the basilar pontine nuclei and nucleus reticularis tegmenti pontis as demonstrated with PHA-L tracing in the rat.Journal of Comparative Neurology, 330, 130–146.
Nicholson, D.A., & Freeman, J.H., Jr. (2002). Neuronal correlates of conditioned inhibition of the eyeblink response in the anterior interpositus nucleus.Behavioral Neuroscience, 116, 22–36.
Nicholson, D.A., & Freeman, J.H., Jr. (2003a). Addition of inhibition in the olivocerebellar system and the ontogeny of a motor memory.Nature Neuroscience, 6, 532–537.
Nicholson, D.A., & Freeman, J.H., Jr. (2003b)., Developmental changes in evoked Purkinje cell complex spike responses.Journal of Neurophysiology, 90, 2349–2357.
Nicholson, D.A., & Freeman, J.H., Jr. (2004). Developmental changes in eyeblink conditioning and simple spike activity in the cerebellar cortex.Developmental Psychobiology, 44, 45–57.
Nicholson, D.A., Sweet, J.A., & Freeman, J.H., Jr. (2003). Long-term retention of the classically conditioned eyeblink response in rats.Behavioral Neuroscience, 117, 871–875.
Rogers, R.F., Britton, G.B., & Steinmetz, J.E. (2001). Learning-related interpositus activity is conserved across species as studied during eyeblink conditioning in the rat.Brain Research, 905, 171–177.
Sears, L.L., & Steinmetz, J.E. (1991). Dorsal accessory inferior olive activity diminishes during acquisition of the rabbit classically conditioned eyelid response.Brain Research, 545, 114–122.
Skelton, R.W. (1988). Bilateral cerebellar lesions disrupt conditioned eyelid responses in unrestrained rats.Behavioral Neuroscience, 102, 586–590.
Steinmetz, J.E. (1990). Neuronal activity in the rabbit interpositus nucleus, during classical NM-conditioning with a pontine-nucleus-stimulation CS.Psychological Science, 1, 378–382.
Steinmetz, J.E., Lavond, D.G., & Thompson, R.F. (1985). Classical conditioning of the rabbit eyelid response with mossy fiber stimulation as the conditioned stimulus.Bulletin of the Psychonomic Society, 23, 245–248.
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, 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.
Steinmetz, J.E., & Sengelaub, D.R. (1992). Possible conditioned stimulus pathway for classical eyelid conditioning in rabbits.Behavioral and Neural Biology, 57, 103–115.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Freeman, J.H., Rabinak, C.A. Eyeblink conditioning in rats using pontine stimulation as a conditioned stimulus. Integrative Physiological & Behavioral Science 39, 180–191 (2004). https://doi.org/10.1007/BF02734438
Issue Date:
DOI: https://doi.org/10.1007/BF02734438