Developmental changes in eyeblink conditioning and neuronal activity in the pontine nuclei.

Neuronal activity was recorded in the pontine nuclei of developing rats during eyeblink conditioning on postnatal days 17-18 (P17-P18) or P24-P25. A pretraining session consisted of unpaired presentations of a 300-msec tone conditioned stimulus (CS) and a 10-msec periorbital shock unconditioned stimulus (US). Five paired training sessions followed the unpaired session, consisting of 100 trials of the CS paired with the US. The rats trained on P24-P25 exhibited significantly more conditioned responses (CRs) than the rats trained on P17-P18, although both groups produced CRs by the end of training. Ontogenetic increases in pre-CS and stimulus-elicited activity in the pontine nuclei were observed during the pretraining session and after paired training. The activity of pontine units was greater on trials with CRs relative to trials without CRs in rats trained on P24-P25, but almost no CR-related modulation was observed in the pontine units of rats trained on P17-P18. The findings indicate that pontine neuronal responses to the CS and modulation of pontine activity by the cerebellum and red nucleus undergo substantial postnatal maturation. The developmental changes in pontine neuronal activity might play a significant role in the ontogeny of eyeblink conditioning.

[1]  J. Voogd,et al.  Anterograde tracing of the rat olivocerebellar system with phaseolus vulgaris leucoagglutinin (PHA‐L). Demonstration of climbing fiber collateral innervation of the cerebellar nuclei , 1989, The Journal of comparative neurology.

[2]  C. Yeo,et al.  The Central Distribution of Primary Afferents from the External Eyelids, Conjunctiva, and Cornea in the Rabbit, Studied Using WGA-HRP and B-HRP as Transganglionic Tracers , 1996, Experimental Neurology.

[3]  J. Harvey,et al.  Acute inactivation of the inferior olive blocks associative learning , 1998, The European journal of neuroscience.

[4]  J H Freeman,et al.  Developmental Changes in Eye-Blink Conditioning and Neuronal Activity in the Cerebellar Interpositus Nucleus , 2000, The Journal of Neuroscience.

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

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

[7]  M. Stanton,et al.  Eyeblink conditioning in the developing rat. , 1992, Behavioral Neuroscience.

[8]  M. Garwicz,et al.  Evidence for a GABA-mediated cerebellar inhibition of the inferior olive in the cat , 2004, Experimental Brain Research.

[9]  R. Clark,et al.  Reversible lesions of the cerebellar interpositus nucleus during acquisition and retention of a classically conditioned behavior. , 1992, Behavioral neuroscience.

[10]  Richard F. Thompson,et al.  Neuronal responses of the rabbit brainstem during performance of the classically conditioned nictitating membrane (NM)/eyelid response , 1983, Brain Research.

[11]  R. F. Thompson,et al.  Reacquisition of classical conditioning after removal of cerebellar cortex , 2004, Experimental Brain Research.

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

[13]  R. F. Thompson,et al.  Classical conditioning using stimulation of the inferior olive as the unconditioned stimulus. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Learning- and cerebellum-dependent neuronal activity in the lateral pontine nucleus. , 2000, Behavioral neuroscience.

[15]  M. Mauk,et al.  Pharmacological analysis of cerebellar contributions to the timing and expression of conditioned eyelid responses , 1998, Neuropharmacology.

[16]  Javier F. Medina,et al.  Timing Mechanisms in the Cerebellum: Testing Predictions of a Large-Scale Computer Simulation , 2000, The Journal of Neuroscience.

[17]  R. F. Thompson,et al.  Inhibitory cerebello-olivary projections and blocking effect in classical conditioning. , 1998, Science.

[18]  D. Nicholson,et al.  Ontogenetic changes in the neural mechanisms of eyeblink conditioning , 2001, Integrative physiological and behavioral science : the official journal of the Pavlovian Society.

[19]  R. F. Thompson,et al.  Classical conditioning in rabbits using pontine nucleus stimulation as a conditioned stimulus and inferior olive stimulation as an unconditioned stimulus , 1989, Synapse.

[20]  D. Nicholson,et al.  Neuronal activity in the cerebellar interpositus and lateral pontine nuclei during inhibitory classical conditioning of the eyeblink response , 1999, Brain Research.

[21]  J. Steinmetz,et al.  Acquisition of classical conditioning without cerebellar cortex , 1989, Behavioural Brain Research.

[22]  J. Steinmetz,et al.  Multiple-unit activity from rabbit cerebellar cortex and interpositus nucleus during classical discrimination/reversal eyelid conditioning , 1994, Brain Research.

[23]  T. Land,et al.  Anatomical study of the rabbit's corneal-VIth nerve reflex: Connections between cornea, trigeminal sensory complex, and the abducens and accessory abducens nuclei , 1984, Brain Research.

[24]  J. W. Moore,et al.  Cerebellar Purkinje cell activity related to the classically conditioned nictitating membrane response , 2004, Experimental Brain Research.

[25]  D J Rosen,et al.  Classical conditioning of the rabbit eyelid response with a mossy-fiber stimulation CS: I. Pontine nuclei and middle cerebellar peduncle stimulation. , 1986, Behavioral neuroscience.

[26]  Y Shinoda,et al.  The Entire Trajectories of Single Olivocerebellar Axons in the Cerebellar Cortex and their Contribution to Cerebellar Compartmentalization , 2001, The Journal of Neuroscience.

[27]  Rosalba Parenti,et al.  Projections of the basilar pontine nuclei and nucleus reticularis tegmenti pontis to the cerebellar nuclei of the rat , 2002, The Journal of comparative neurology.

[28]  J E Steinmetz,et al.  Single-unit evidence for eye-blink conditioning in cerebellar cortex is altered, but not eliminated, by interpositus nucleus lesions. , 1997, Learning & memory.

[29]  M. Mauk,et al.  Cerebellar Cortex Lesions Prevent Acquisition of Conditioned Eyelid Responses , 1999, The Journal of Neuroscience.

[30]  Richard F. Thompson Discovering the Brain Substrates of Eyeblink Classical Conditioning , 2002 .

[31]  B G Schreurs Stimulation of the spinal trigeminal nucleus supports classical conditioning of the rabbit's nictitating membrane response. , 1988, Behavioral neuroscience.

[32]  J. Steinmetz Neuronal Activity in the Rabbit Interpositus Nucleus during Classical NM-Conditioning with a Pontine-Nucleus-Stimulation CS , 1990 .

[33]  R. F. Thompson,et al.  Neuronal responses of the rabbit cerebellum during acquisition and performance of a classically conditioned nictitating membrane-eyelid response , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[34]  Narender Ramnani,et al.  Reversible inactivations of the cerebellum with muscimol prevent the acquisition and extinction of conditioned nictitating membrane responses in the rabbit , 1996, Experimental Brain Research.

[35]  G. A. Clark,et al.  Effects of lesions of cerebellar nuclei on conditioned behavioral and hippocampal neuronal responses , 1984, Brain Research.

[36]  G. Hesslow,et al.  Suppression of cerebellar Purkinje cells during conditioned responses in ferrets. , 1994, Neuroreport.

[37]  C. Yeo,et al.  Cerebellar cortex and eyeblink conditioning: A reexamination , 2004, Experimental Brain Research.

[38]  J E Steinmetz,et al.  Possible conditioned stimulus pathway for classical eyelid conditioning in rabbits. I. Anatomical evidence for direct projections from the pontine nuclei to the cerebellar interpositus nucleus. , 1992, Behavioral and neural biology.

[39]  S. T. Kitai,et al.  Electrophysiological and horseradish peroxidase studies of precerebellar afferents to the nucleus interpositus anterior. I. Climbing fiber system , 1977, Brain Research.

[40]  D J Krupa,et al.  Reversible inactivation of the cerebellar interpositus nucleus completely prevents acquisition of the classically conditioned eye-blink response. , 1997, Learning & memory.

[41]  M. Glickstein,et al.  Classical conditioning of the nictitating membrane response of the rabbit , 2004, Experimental Brain Research.

[42]  L. Aitkin,et al.  Acoustic input to the lateral pontine nuclei , 1978, Hearing Research.

[43]  R. F. Thompson,et al.  Organization of memory traces in the mammalian brain. , 1994, Annual review of neuroscience.

[44]  M. Gabriel,et al.  Stimulus-related and movement-related single-unit activity in rabbit cingulate cortex and limbic thalamus during performance of discriminative avoidance behavior , 1996, Brain Research.

[45]  Richard F. Thompson,et al.  Localization of a memory trace in the mammalian brain. , 1993, Science.

[46]  R. F. Thompson,et al.  Initial localization of the acoustic conditioned stimulus projection system to the cerebellum essential for classical eyelid conditioning. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[47]  R. Skelton,et al.  Bilateral cerebellar lesions disrupt conditioned eyelid responses in unrestrained rats. , 1988, Behavioral neuroscience.

[48]  G. Hesslow,et al.  Inhibition of the inferior olive during conditioned responses in the decerebrate ferret , 1996, Experimental Brain Research.

[49]  C I De Zeeuw,et al.  Climbing fibre collaterals contact neurons in the cerebellar nuclei that provide a GABAergic feedback to the inferior olive. , 1997, Neuroscience.

[50]  Christopher H. Yeo,et al.  Cerebellar Function in Consolidation of a Motor Memory , 2002, Neuron.

[51]  R. Clark,et al.  The learning-related activity that develops in the pontine nuclei during classical eye-blink conditioning is dependent on the interpositus nucleus. , 1997, Learning & memory.

[52]  Richard F. Thompson,et al.  Effects of lidocaine injection in the interpositus nucleus and red nucleus on conditioned behavioral and neuronal responses , 1990, Brain Research.

[53]  Richard F. Thompson,et al.  Cerebellar cortical inhibition and classical eyeblink conditioning , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[54]  G. Mihailoff Cerebellar nuclear projections from the basilar pontine nuclei and nucleus reticularis tegmenti pontis as demonstrated with PHA‐L tracing in the rat , 1993, The Journal of comparative neurology.

[55]  R. F. Thompson,et al.  Disruption of classical eyelid conditioning after cerebellar lesions: damage to a memory trace system or a simple performance deficit? , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[56]  Joseph E. Steinmetz,et al.  Classical conditioning of the rabbit eyelid response with mossy fiber stimulation as the conditioned stimulus , 1985 .

[57]  Richard F. Thompson,et al.  Lesions of the inferior olivary complex cause extinction of the classically conditioned eyeblink response , 1985, Brain Research.

[58]  Richard F. Thompson,et al.  The Nature of Reinforcement in Cerebellar Learning , 1998, Neurobiology of Learning and Memory.

[59]  C. Yeo,et al.  Acquisition of Eyeblink Conditioning Is Critically Dependent on Normal Function in Cerebellar Cortical Lobule HVI , 2001, The Journal of Neuroscience.

[60]  D. Lavond,et al.  The effects of reversible inactivation of the red nucleus on learning-related and auditory-evoked unit activity in the pontine nuclei of classically conditioned rabbits. , 1997, Learning & memory.

[61]  G. A. Clark,et al.  Initial localization of the memory trace for a basic form of learning. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[62]  T. Voneida,et al.  Changes in instrumentally and classically conditioned limb-flexion responses following inferior olivary lesions and olivocerebellar tractotomy in the cat , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[63]  R. F. Thompson,et al.  Effect of kainic acid lesions of the cerebellar interpositus nucleus on eyelid conditioning in the rabbit , 1985, Brain Research.

[64]  M. Mauk,et al.  Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[65]  D. Nicholson,et al.  Developmental Changes in Eye-Blink Conditioning and Neuronal Activity in the Inferior Olive , 2000, The Journal of Neuroscience.

[66]  J. Steinmetz,et al.  Dorsal accessory inferior olive activity diminishes during acquisition of the rabbit classically conditioned eyelid response , 1991, Brain Research.

[67]  D. Nicholson,et al.  Neuronal correlates of conditioned inhibition of the eyeblink response in the anterior interpositus nucleus. , 2002, Behavioral neuroscience.

[68]  J. W. Moore,et al.  Activity of deep cerebellar nuclear cells during classical conditioning of nictitating membrane extension in rabbits , 2004, Experimental Brain Research.

[69]  J. Steinmetz,et al.  Possible CS and US pathways for rabbit classical eyelid conditioning: electrophysiological evidence for projections from the pontine nuclei and inferior olive to cerebellar cortex and nuclei. , 1993, Behavioral and neural biology.

[70]  M. Mauk,et al.  Inhibition of climbing fibres is a signal for the extinction of conditioned eyelid responses , 2002, Nature.

[71]  D. Nicholson,et al.  Addition of inhibition in the olivocerebellar system and the ontogeny of a motor memory , 2003, Nature Neuroscience.

[72]  R. Llinás,et al.  GABAergic modulation of complex spike activity by the cerebellar nucleoolivary pathway in rat. , 1996, Journal of neurophysiology.