Abstract
During eyeblink conditioning, Purkinje cells that control blinking develop an inhibitory response to the conditional stimulus. This conditional response (CR) in the Purkinje cell shows a number of striking similarities to the overt blink CR, including adaptive timing. The evidence suggests that the Purkinje cell CR drives the overt CR. Recent results show that the Purkinje cell CR does not depend on long-term depression but on a novel mechanism that enables the cell to learn the temporal interval between conditional and unconditional stimuli and time of the CR accordingly.
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References
Albus J (1971) A theory of cerebellar function. Math Biosci 10:25–61
Berthier NE, Moore JW (1986) Cerebellar Purkinje cell activity related to the classically conditioned nictitating membrane response. Exp Brain Res 63(2):341–350
Gallistel CR, Matzel LD (2013) The neuroscience of learning: beyond the Hebbian synapse. Annu Rev Psychol 64:169–200. https://doi.org/10.1146/annurev-psych-113011-143807
Gormezano I, Moore JW (1969) Classical conditioning. In: Marx MH (ed) Learning: processes. Macmillan, New York
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(1):17–34
Green JT, Steinmetz JE (2005) Purkinje cell activity in the cerebellar anterior lobe after rabbit eyeblink conditioning. Learn Mem 12(3):260–269
Halverson HE, Khilkevich A, Mauk MD (2015) Relating cerebellar purkinje cell activity to the timing and amplitude of conditioned eyelid responses. J Neurosci 35(20):7813–7832. https://doi.org/10.1523/JNEUROSCI.3663-14.2015
Hansel C, Linden DJ, D’Angelo E (2001) Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity in the cerebellum. Nat Neurosci 4(5):467–475. https://doi.org/10.1038/87419
Harvey RJ, Napper RMA (1991) Quantitative studies on the mammalian cerebellum. Prog Neurobiol 36:437–463
Heiney SA, Kim J, Augustine GJ, Medina JF (2014a) Precise control of movement kinematics by optogenetic inhibition of Purkinje cell activity. J Neurosci 34(6):2321–2330. https://doi.org/10.1523/JNEUROSCI.4547-13.2014
Heiney SA, Wohl MP, Chettih SN, Ruffolo LI, Medina JF (2014b) Cerebellar-dependent expression of motor learning during eyeblink conditioning in head-fixed mice. J Neurosci 34(45):14845–14853. https://doi.org/10.1523/JNEUROSCI.2820-14.2014
Heiney SA, Ohmae S, Kim OA, Medina JF (2018) Single-unit extracellular recording from the cerebellum during eyeblink conditioning in head-fixed mice. In: Sillitoe RV (ed) Extracellular recording approaches. Springer New York, New York, pp 39–71. https://doi.org/10.1007/978-1-4939-7549-5_3
Hesslow G (1994a) Correspondence between climbing fibre input and motor output in eyeblink-related areas in cat cerebellar cortex. J Physiol Lond 476(2):229–244
Hesslow G (1994b) Inhibition of classically conditioned eyeblink responses by stimulation of the cerebellar cortex in the decerebrate cat. J Physiol Lond 476(2):245–256
Hesslow G (1995) Classical conditioning of eyeblink in decerebrate cats and ferrets. In: Ferrell WR, Proske U (eds) Neural control of movement. Plenum Press, New York, pp 117–122
Hesslow G, Ivarsson M (1994) Suppression of cerebellar Purkinje cells during conditioned responses in ferrets. Neuroreport 5(5):649–652
Hesslow G, Yeo CH (2002) The functional anatomy of skeletal conditioning. In: Moore JW (ed) A neuroscientist’s guide to classical conditioning. Springer, New York, pp 86–146
Hesslow G, Jirenhed D-A, Rasmussen A, Johansson F (2013) Classical conditioning of motor responses: what is the learning mechanism? Neural Netw 47:81–87. https://doi.org/10.1016/j.neunet.2013.03.013
Hoehler FK, Leonard DW (1976) Double responding in classical nictitating membrane conditioning with single-CS dual-ISI training. Pavlov J Biol Sci 11:180–190
Jirenhed DA, Hesslow G (2011a) Learning stimulus intervals--adaptive timing of conditioned purkinje cell responses. Cerebellum 10(3):523–535. https://doi.org/10.1007/s12311-011-0264-3
Jirenhed DA, Hesslow G (2011b) Time course of classically conditioned Purkinje cell response is determined by initial part of conditioned stimulus. J Neurosci 31(25):9070–9074. https://doi.org/10.1523/JNEUROSCI.1653-11.2011
Jirenhed DA, Hesslow G (2016) Are Purkinje cell pauses drivers of classically conditioned blink responses? Cerebellum 15(4):526–534. https://doi.org/10.1007/s12311-015-0722-4
Jirenhed DA, Bengtsson F, Hesslow G (2007) Acquisition, extinction, and reacquisition of a cerebellar cortical memory trace. J Neurosci 27(10):2493–2502. https://doi.org/10.1523/JNEUROSCI.4202-06.2007
Jirenhed D-A, Rasmussen A, Johansson F, Hesslow G (2017) Learned response sequences in cerebellar Purkinje cells. Proc Natl Acad Sci USA 114(23):6127–6132. https://doi.org/10.1073/pnas.1621132114
Johansson F, Jirenhed DA, Rasmussen A, Zucca R, Hesslow G (2014) Memory trace and timing mechanism localized to cerebellar Purkinje cells. Proc Natl Acad Sci USA 111(41):14930–14934. https://doi.org/10.1073/pnas.1415371111
Johansson F, Carlsson HAE, Rasmussen A, Yeo CH, Hesslow G (2015) Activation of a temporal memory in Purkinje cells by the mGluR7 receptor. Cell Rep 13(9):1741–1746. https://doi.org/10.1016/j.celrep.2015.10.047
Johansson F, Jirenhed DA, Rasmussen A, Zucca R, Hesslow G (2018) Absence of parallel fibre to Purkinje cell LTD during eyeblink conditioning. Sci Rep 8(1):14777. https://doi.org/10.1038/s41598-018-32791-7
Kehoe EJ, Macrae M (2002) Fundamental behavioral methods and findings in classical conditioning. In: Moore JW (ed) A neuroscientist’s guide to classical conditioning. Springer, New York, pp 171–231
Kotani S, Kawahara S, Kirino Y (2003) Purkinje cell activity during learning a new timing in classical eyeblink conditioning. Brain Res 994(2):193–202
Kotani S, Kawahara S, Kirino Y (2006) Purkinje cell activity during classical eyeblink conditioning in decerebrate guinea pigs. Brain Res 1068(1):70–81
Longley M, Yeo CH (2014) Distribution of neural plasticity in cerebellum- dependent motor learning. Prog Brain Res 210:79
Mauk MD, Buonomano DV (2004) The neural basis of temporal processing. Annu Rev Neurosci 27:307–340
Medina JF, Mauk MD (2000) Computer simulation of cerebellar information processing. Nat Neurosci 3:1205–1211
Millenson JR, Kehoe EJ, Gormezano I (1977) Classical conditioning of the rabbit’s nictitating membrane response under fixed and mixed CS-US intervals. Learn Motiv 8:351–366
Ohmae S, Medina JF (2015) Climbing fibers encode a temporal-difference prediction error during cerebellar learning in mice. Nat Neurosci 18(12):1798–1803. https://doi.org/10.1038/nn.4167
Rasmussen A, Jirenhed DA, Hesslow G (2008) Simple and complex spike firing patterns in Purkinje cells during classical conditioning. Cerebellum 7(4):563–566. https://doi.org/10.1007/s12311-008-0068-2
Rasmussen A, Jirenhed D-A, Zucca R, Johansson F, Svensson P, Hesslow G (2013) Number of spikes in climbing fibers determines the direction of cerebellar learning. J Neurosci 33(33):13436–13440. https://doi.org/10.1523/JNEUROSCI.1527-13.2013
Rasmussen A, Jirenhed DA, Wetmore DZ, Hesslow G (2014) Changes in complex spike activity during classical conditioning. Front Neural Circuits 8:90. https://doi.org/10.3389/fncir.2014.00090
Rasmussen A, Zucca R, Johansson F, Jirenhed DA, Hesslow G (2015) Purkinje cell activity during classical conditioning with different conditional stimuli explains central tenet of Rescorla-Wagner model. Proc Natl Acad Sci USA 112(45):14060–14065. https://doi.org/10.1073/pnas.1516986112
Salafia WR, Lambert RW, Host KC, Chiala NL, Ramirez JJ (1980) Rabbit nictitating membrane conditioning: lower limit of the effective interstimulus interval. Anim Learn Behav 8:85–91
Schneiderman N, Gormezano I (1964) Conditioning of the nictitating membrane of the rabbit as a function of the CS-US interval. J Comp Physiol Psychol 57:188–195
Svensson P, Ivarsson M (1999) Short-lasting conditioned stimulus applied to the middle cerebellar peduncle elicits delayed conditioned eye blink responses in the decerebrate ferret. Eur J Neurosci 11(12):4333–4340
Svensson P, Ivarsson M, Hesslow G (1997) Effect of varying the intensity and train frequency of forelimb and cerebellar mossy fiber conditioned stimuli on the latency of conditioned eye-blink responses in decerebrate ferrets. Learn Mem 4(1):105–115
Svensson P, Jirenhed DA, Bengtsson F, Hesslow G (2010) Effect of conditioned stimulus parameters on timing of conditioned Purkinje cell responses. J Neurophysiol 103(3):1329–1336. https://doi.org/10.1152/jn.00524.2009
Ten Brinke MM, Boele HJ, Spanke JK, Potters JW, Kornysheva K, Wulff P, IJpelaar ACHG, Koekkoek SK, De Zeeuw CI (2015) Evolving models of Pavlovian conditioning: cerebellar cortical dynamics in awake behaving mice. Cell Rep 13(9):1977–1988. https://doi.org/10.1016/j.celrep.2015.10.057
Thompson RF, Steinmetz JE (2009) The role of the cerebellum in classical conditioning of discrete behavioral responses. Neuroscience 162:732–755
Tracy JA, Steinmetz JE (1998) Purkinje cell responses to pontine stimulation CS during rabbit eyeblink conditioning. Physiol Behav 65(2):381–386
Wetmore DZ, Jirenhed D-A, Rasmussen A, Johansson F, Schnitzer MJ, Hesslow G (2014) Bidirectional plasticity of Purkinje cells matches temporal features of learning. J Neurosci 34(5):1731–1737. https://doi.org/10.1523/JNEUROSCI.2883-13.2014
Yamazaki T, Tanaka S (2009) Computational models of timing mechanisms in the cerebellar granular layer. Cerebellum 8:423–432
Acknowledgments
This work was supported by grants from the Swedish Research Council to G.H. (2018-03191), to F.J. (2016-00127) and to the Linnaeus project “Thinking in Time: Cognition, Communication and Learning” (349-2007-8695), and grants from the Thorsten Söderberg foundation.
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Hesslow, G., Jirenhed, DA., Johansson, F. (2022). Purkinje Neurons During Eye Blink Conditioning and New Mechanisms of Cerebellar Learning and Timing. In: Manto, M.U., Gruol, D.L., Schmahmann, J.D., Koibuchi, N., Sillitoe, R.V. (eds) Handbook of the Cerebellum and Cerebellar Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-23810-0_115
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