Learning Stimulus Intervals—Adaptive Timing of Conditioned Purkinje Cell Responses

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.

[1]  F K Hoehler,et al.  Double responding in classical nictitating membrane conditioning with single-CS dual-ISI training , 1976, The Pavlovian journal of biological science.

[2]  J. R. Millenson,et al.  Classical conditioning of the rabbit's nictitating membrane response under fixed and mixed CS-US intervals , 1977 .

[3]  R. F. Thompson,et al.  Cerebellum: essential involvement in the classically conditioned eyelid response. , 1984, Science.

[4]  D. Zipser.  A model of hippocampal learning during classical conditioning. , 1986, Behavioral neuroscience.

[5]  J Schouenborg,et al.  Climbing fibres projecting to cat cerebellar anterior lobe activated by cutaneous A and C fibres. , 1987, The Journal of physiology.

[6]  G. Hesslow.  Inhibition of classically conditioned eyeblink responses by stimulation of the cerebellar cortex in the decerebrate cat. , 1994, The Journal of physiology.

[7]  G. Hesslow.  Correspondence between climbing fibre input and motor output in eyeblink‐related areas in cat cerebellar cortex. , 1994, The Journal of physiology.

[8]  Douglas R. Wylie,et al.  More on climbing fiber signals and their consequence(s) , 1996 .

[9]  S. Grossberg,et al.  Metabotropic Glutamate Receptor Activation in Cerebellar Purkinje Cells as Substrate for Adaptive Timing of the Classically Conditioned Eye-Blink Response , 1996, The Journal of Neuroscience.

[10]  Richard lvry,et al.  Cerebellar timing systems. , 1997 .

[11]  R. Ivry.  Cerebellar timing systems. , 1997, International review of neurobiology.

[12]  Germund Hesslow,et al.  Cerebellum and conditioned reflexes , 1998, Trends in Cognitive Sciences.

[13]  G. Hesslow,et al.  Learned Movements Elicited by Direct Stimulation of Cerebellar Mossy Fiber Afferents , 1999, Neuron.

[14]  E. Kehoe.  Extension of the CS past the US can facilitate conditioning of the rabbit’s nictitating membrane response , 2000, Behavioural Processes.

[15]  Javier F. Medina,et al.  Computer simulation of cerebellar information processing , 2000, Nature Neuroscience.

[16]  E. Kehoe,et al.  Fundamental Behavioral Methods and Findings in Classical Conditioning , 2002 .

[17]  Germund Hesslow,et al.  The Functional Anatomy of Skeletal Conditioning , 2002 .

[18]  S. Kotani,et al.  Purkinje cell activity during learning a new timing in classical eyeblink conditioning , 2003, Brain Research.

[19]  Richard F. Thompson,et al.  Neural substrates of eyeblink conditioning: acquisition and retention. , 2003, Learning & memory.

[20]  June-Seek Choi,et al.  Cerebellar neuronal activity expresses the complex topography of conditioned eyeblink responses. , 2003, Behavioral neuroscience.

[21]  J. W. Moore,et al.  Adaptive timing in neural networks: The conditioned response , 1988, Biological Cybernetics.

[22]  D. Buonomano,et al.  The neural basis of temporal processing. , 2004, Annual review of neuroscience.

[23]  David J. Willshaw,et al.  A Biophysical Model of Synaptic Delay Learning and Temporal Pattern Recognition in a Cerebellar Purkinje Cell , 2004, Journal of Computational Neuroscience.

[24]  R. Ivry,et al.  The neural representation of time , 2004, Current Opinion in Neurobiology.

[25]  J. W. Moore,et al.  Adaptively timed conditioned responses and the cerebellum: A neural network approach , 1989, Biological Cybernetics.

[26]  M. Garwicz,et al.  Anatomical and physiological foundations of cerebellar information processing , 2005, Nature Reviews Neuroscience.

[27]  E. Kehoe,et al.  Temporally specific extinction of conditioned responses in the rabbit (Oryctolagus cuniculus) nictitating membrane preparation. , 2005, Behavioral neuroscience.

[28]  Henrik Jörntell,et al.  Properties of Somatosensory Synaptic Integration in Cerebellar Granule Cells In Vivo , 2006, The Journal of Neuroscience.

[29]  R. A. Hensbroek,et al.  Intraburst and Interburst Signaling by Climbing Fibers , 2007, The Journal of Neuroscience.

[30]  G. Hesslow,et al.  Acquisition, Extinction, and Reacquisition of a Cerebellar Cortical Memory Trace , 2007, The Journal of Neuroscience.

[31]  P. Dean,et al.  Evidence from retractor bulbi EMG for linearized motor control of conditioned nictitating membrane responses. , 2007, Journal of neurophysiology.

[32]  Nestor A. Schmajuk,et al.  Classical conditioning , 2008, Scholarpedia.

[33]  Richard F. Thompson,et al.  The role of the cerebellum in classical conditioning of discrete behavioral responses , 2009, Neuroscience.

[34]  Shigeru Tanaka,et al.  Computational Models of Timing Mechanisms in the Cerebellar Granular Layer , 2009, The Cerebellum.

[35]  Elliot A. Ludvig,et al.  Timing in trace conditioning of the nictitating membrane response of the rabbit (Oryctolagus cuniculus): scalar, nonscalar, and adaptive features. , 2010, Learning & memory.

[36]  G. Hesslow,et al.  Effect of conditioned stimulus parameters on timing of conditioned Purkinje cell responses. , 2010, Journal of neurophysiology.