Abstract
Classical conditioning of motor responses, such as the eyeblink response, is an experimental model of associative learning and of adaptive timing of movements. A conditioned blink will have its maximum amplitude near the expected onset of the unconditioned blink-eliciting stimulus and it adapts to changes in the interval between the conditioned and unconditioned stimuli. Previous studies have shown that an eyeblink conditioning protocol can make cerebellar Purkinje cells learn to pause in response to the conditioned stimulus. According to the cerebellar cortical conditioning model, this conditioned Purkinje cell response drives the overt blink. If so, the model predicts that the temporal properties of the Purkinje cell response reflect the overt behaviour. To test this prediction, in vivo recordings of Purkinje cell activity were performed in decerebrate ferrets during conditioning, using direct stimulation of cerebellar mossy and climbing fibre afferents as conditioned and unconditioned stimuli. The results show that Purkinje cells not only develop a change in responsiveness to the conditioned stimulus. They also learn a particular temporal response profile where the timing, not only of onset and maximum but also of offset, is determined by the temporal interval between the conditioned and unconditioned stimuli.
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References
Kehoe EJ, Macrae M. Fundamental behavioral methods and findings in classical conditioning. In: Moore JW, editor. A neuroscientist’s guide to classical conditioning. New York: Springer; 2002. p. 171–231.
Mauk MD, Buonomano DV. The neural basis of temporal processing. Annu Rev Neurosci. 2004;27:307–40.
Ivry R. Cerebellar timing systems. In: Schmahmann JD, editor. The cerebellum and cognition. New York: Academic; 1997. p. 555–73.
Ivry RB, Spencer RM. The neural representation of time. Curr Opin Neurobiol. 2004;14(2):225–32.
McCormick DA, Thompson RF. Cerebellum: essential involvement in the classically conditioned eyelid response. Science. 1984;223(4633):296–9.
Hesslow G, Yeo CH. The functional anatomy of skeletal conditioning. In: Moore JW, editor. A neuroscientist’s guide to classical conditioning. New York: Springer; 2002. p. 86–146.
Christian KM, Thompson RF. Neural substrates of eyeblink conditioning: acquisition and retention. Learn Mem. 2003;10(6):427–55.
Thompson RF, Steinmetz JE. The role of the cerebellum in classical conditioning of discrete behavioral responses. Neuroscience. 2009;162(3):732–55.
Jirenhed DA, Bengtsson F, Hesslow G. Acquisition, extinction, and reacquisition of a cerebellar cortical memory trace. J Neurosci. 2007;27(10):2493–502.
Yeo CH, Hesslow G. Cerebellum and conditioned reflexes. Trends Cogn Sci. 1998;2(9):322–30.
Kotani S, Kawahara S, Kirino Y. Purkinje cell activity during learning a new timing in classical eyeblink conditioning. Brain Res. 2003;994(2):193–202.
Ekerot CF, Gustavsson P, Oscarsson O, Schouenborg J. Climbing fibres projecting to cat cerebellar anterior lobe activated by cutaneous A and C fibres. J Physiol Lond. 1987;386:529–38.
Simpson JI, Wylie DR, De Zeeuw CI. On climbing fiber signals and their consequences. Behav Brain Sci. 1996;19:384–98.
Maruta J, Hensbroek RA, Simpson JI. Intraburst and interburst signaling by climbing fibers. J Neurosci. 2007;27(42):11263–70.
Hesslow G. Correspondence between climbing fibre input and motor output in eyeblink-related areas in cat cerebellar cortex. J Physiol Lond. 1994;476(2):229–44.
Hesslow G. Inhibition of classically conditioned eyeblink responses by stimulation of the cerebellar cortex in the decerebrate cat. J Physiol Lond. 1994;476(2):245–56.
Kehoe EJ. Extension of the CS past the US can facilitate conditioning of the rabbit’s nictitating membrane response. Behav Processes. 2000;50(2–3):155–64.
Gormezano I, Moore JW. Classical conditioning. In: Marx MH, editor. Learning: processes. New York: Macmillan; 1969.
Lepora NF, Mavritsaki E, Porrill J, Yeo CH, Evinger C, Dean P. Evidence from retractor bulbi EMG for linearized motor control of conditioned nictitating membrane responses. J Neurophysiol. 2007;98(4):2074–88.
Kehoe EJ, Joscelyne A. Temporally specific extinction of conditioned responses in the rabbit (Oryctolagus cuniculus) nictitating membrane preparation. Behav Neurosci. 2005;119:1011–22.
Apps R, Garwicz M. Anatomical and physiological foundations of cerebellar information processing. Nat Rev Neurosci. 2005;6:297–311.
Kehoe EJ, Ludvig EA, Sutton RS. Timing in trace conditioning of the nictitating membrane response of the rabbit (Oryctolagus cuniculus): scalar, nonscalar, and adaptive features. Learn Mem. 2010;17(12):600–4.
Millenson JR, Kehoe EJ, Gormezano I. Classical conditioning of the rabbit’s nictitating membrane response under fixed and mixed CS–US intervals. Learn Motiv. 1977;8:351–66.
Hoehler FK, Leonard DW. Double responding in classical nictitating membrane conditioning with single-CS dual-ISI training. Pavlov J Biol Sci. 1976;11:180–90.
Choi JS, Moore JW. Cerebellar neuronal activity expresses the complex topography of conditioned eyeblink responses. Behav Neurosci. 2003;117(6):1211–9.
Yamazaki T, Tanaka S. Computational models of timing mechanisms in the cerebellar granular layer. Cerebellum. 2009;8(4):423–32.
Fiala JC, Grossberg S, Bullock D. Metabotropic glutamate receptor activation in cerebellar Purkinje cells as substrate for adaptive timing of the classically conditioned eye-blink response. J Neurosci. 1996;16(11):3760–74.
Steuber V, Willshaw D. A biophysical model of synaptic delay learning and temporal pattern recognition in a cerebellar Purkinje cell. J Comput Neurosci. 2004;17:149–64.
Desmond JE, Moore JW. Adaptive timing in neural networks: the conditioned response. Biol Cybern. 1988;58(6):405–15.
Zipser D. A model of hippocampal learning during classical conditioning. Behav Neurosci. 1986;100(5):764–76.
Hesslow G, Svensson P, Ivarsson M. Learned movements elicited by direct stimulation of cerebellar mossy fiber afferents. Neuron. 1999;24(1):179–85.
Svensson P, Jirenhed DA, Bengtsson F, Hesslow G. Effect of conditioned stimulus parameters on timing of conditioned Purkinje cell responses. J Neurophysiol. 2010;103(3):1329–36.
Medina JF, Mauk MD. Computer simulation of cerebellar information processing. Nat Neurosci. 2000;3:1205–11.
Moore JW, Desmond JE, Berthier NE. Adaptively timed conditioned responses and the cerebellum: a neural network approach. Biol Cybern. 1989;62(1):17–28.
Jörntell H, Ekerot CF. Properties of somatosensory synaptic integration in cerebellar granule cells in vivo. J Neurosci. 2006;26(45):11786–97.
Acknowledgements
This work was supported by grants from the Swedish Research Council to The Linnaeus Centre for Cognition, Communication and Learning at Lund University (349-2007-8695) and to G. Hesslow (09899) and the Söderberg and Åhlen foundations.
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Jirenhed, DA., Hesslow, G. Learning Stimulus Intervals—Adaptive Timing of Conditioned Purkinje Cell Responses. Cerebellum 10, 523–535 (2011). https://doi.org/10.1007/s12311-011-0264-3
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DOI: https://doi.org/10.1007/s12311-011-0264-3