REM sleep twitches rouse nascent cerebellar circuits: Implications for sensorimotor development

The cerebellum is critical for sensorimotor integration and undergoes extensive postnatal development. During the first postnatal week in rats, climbing fibers polyinnervate Purkinje cells and, before granule cell migration, mossy fibers make transient, direct connections with Purkinje cells. Activity‐dependent processes are assumed to play a critical role in the development and refinement of these and other aspects of cerebellar circuitry. However, the sources and patterning of activity have not been described. We hypothesize that sensory feedback (i.e., reafference) from myoclonic twitches in sleeping newborn rats is a prominent driver of activity for the developing cerebellum. Here, in 6‐day‐old rats, we show that Purkinje cells exhibit substantial state‐dependent changes in complex and simple spike activity—primarily during active sleep. In addition, this activity increases significantly during bouts of twitching. Moreover, the surprising observation of twitch‐dependent increases in simple spike activity at this age suggests a functional engagement of mossy fibers before the parallel fiber system has developed. Based on these and other results, we propose that twitching comprises a unique class of self‐produced movement that drives critical aspects of activity‐dependent development in the cerebellum and other sensorimotor systems. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 1140–1153, 2015

[1]  Mitchel T. Williams.  Oxford Handbook of Developmental Behavioral Neuroscience, Mark Blumberg, John Freeman, Scott Robinson (Eds.). Oxford University Press, New York, NY (2010), [769 pages, US $135.00], ISBN: 978-0-19-531473-1 , 2014 .

[2]  B. McMurray,et al.  Spatiotemporal Structure of REM Sleep Twitching Reveals Developmental Origins of Motor Synergies , 2013, Current Biology.

[3]  M. Kano,et al.  Synapse elimination in the developing cerebellum , 2013, Cellular and Molecular Life Sciences.

[4]  K. Deisseroth,et al.  Arc/Arg3.1 Is a Postsynaptic Mediator of Activity-Dependent Synapse Elimination in the Developing Cerebellum , 2013, Neuron.

[5]  H. G. Marques,et al.  Twitching in Sensorimotor Development from Sleeping Rats to Robots , 2013, Current Biology.

[6]  Adam W Hantman,et al.  Convergence of pontine and proprioceptive streams onto multimodal cerebellar granule cells , 2013, eLife.

[7]  M. Blumberg,et al.  Rapid Whisker Movements in Sleeping Newborn Rats , 2012, Current Biology.

[8]  M. Crair,et al.  Retinal waves coordinate patterned activity throughout the developing visual system , 2012, Nature.

[9]  Timothy H Murphy,et al.  Voltage-Sensitive Dye Imaging Reveals Dynamic Spatiotemporal Properties of Cortical Activity after Spontaneous Muscle Twitches in the Newborn Rat , 2012, The Journal of Neuroscience.

[10]  Asohan Amarasingham,et al.  Conditional modeling and the jitter method of spike resampling. , 2012, Journal of neurophysiology.

[11]  Patrick O Kanold,et al.  Subplate Neurons Promote Spindle Bursts and Thalamocortical Patterning in the Neonatal Rat Somatosensory Cortex , 2012, The Journal of Neuroscience.

[12]  M. Kano,et al.  Activity-Dependent Maturation of Climbing Fiber to Purkinje Cell Synapses during Postnatal Cerebellar Development , 2011, The Cerebellum.

[13]  Masahiko Watanabe,et al.  Climbing fiber synapse elimination in cerebellar Purkinje cells , 2011, The European journal of neuroscience.

[14]  Carol A. Mason,et al.  Development of Axon-Target Specificity of Ponto-Cerebellar Afferents , 2011, PLoS biology.

[15]  D. E.Vonholstan,et al.  The Principle of Reafference : Interactions Between the Central Nervous System and the Peripheral Organs , 2011 .

[16]  M. Blumberg.  Beyond Dreams: Do Sleep-Related Movements Contribute to Brain Development? , 2010, Front. Neur..

[17]  M. Blumberg,et al.  Developmental appearance and disappearance of cortical events and oscillations in infant rats , 2010, Brain Research.

[18]  M. Blumberg,et al.  Neocortical Activation of the Hippocampus during Sleep in Infant Rats , 2010, The Journal of Neuroscience.

[19]  Scott R. Robinson,et al.  Oxford handbook of developmental behavioral neuroscience , 2009 .

[20]  Jyh-Jang Sun,et al.  Three Patterns of Oscillatory Activity Differentially Synchronize Developing Neocortical Networks In Vivo , 2009, The Journal of Neuroscience.

[21]  Stuart Geman,et al.  A Rate and History-Preserving Resampling Algorithm for Neural Spike Trains , 2009, Neural Computation.

[22]  H. Luhmann,et al.  Cellular mechanisms of subplate-driven and cholinergic input-dependent network activity in the neonatal rat somatosensory cortex. , 2009, Cerebral cortex.

[23]  M. Blumberg,et al.  Synchronous Bursts of Neuronal Activity in the Developing Hippocampus: Modulation by Active Sleep and Association with Emerging Gamma and Theta Rhythms , 2008, The Journal of Neuroscience.

[24]  M. Blumberg,et al.  The corpus callosum modulates spindle‐burst activity within homotopic regions of somatosensory cortex in newborn rats , 2008, The European journal of neuroscience.

[25]  M. Sommer,et al.  Corollary discharge across the animal kingdom , 2008, Nature Reviews Neuroscience.

[26]  J. Freeman,et al.  Eyeblink conditioning in 12-day-old rats using pontine stimulation as the conditioned stimulus , 2008, Proceedings of the National Academy of Sciences.

[27]  M. Blumberg,et al.  The microstructure of active and quiet sleep as cortical delta activity emerges in infant rats. , 2008, Sleep.

[28]  J. Ford,et al.  Out-of-Synch and Out-of-Sorts: Dysfunction of Motor-Sensory Communication in Schizophrenia , 2008, Biological Psychiatry.

[29]  N. Tritsch,et al.  The origin of spontaneous activity in the developing auditory system , 2007, Nature.

[30]  A. Joyner,et al.  Morphology, molecular codes, and circuitry produce the three-dimensional complexity of the cerebellum. , 2007, Annual review of cell and developmental biology.

[31]  Jochen F Staiger,et al.  Cholinergic Modulation of Spindle Bursts in the Neonatal Rat Visual Cortex In Vivo , 2007, The Journal of Neuroscience.

[32]  J. Poulet,et al.  New insights into corollary discharges mediated by identified neural pathways , 2007, Trends in Neurosciences.

[33]  Richard Apps,et al.  Precise Spatial Relationships between Mossy Fibers and Climbing Fibers in Rat Cerebellar Cortical Zones , 2006, The Journal of Neuroscience.

[34]  Yehezkel Ben-Ari,et al.  Retinal Waves Trigger Spindle Bursts in the Neonatal Rat Visual Cortex , 2006, The Journal of Neuroscience.

[35]  S. Blakemore,et al.  The ability to self-tickle following Rapid Eye Movement sleep dreaming , 2006, Consciousness and Cognition.

[36]  M. Blumberg,et al.  The preoptic hypothalamus and basal forebrain play opposing roles in the descending modulation of sleep and wakefulness in infant rats , 2006, The European journal of neuroscience.

[37]  M. Blumberg,et al.  Active medullary control of atonia in week-old rats , 2005, Neuroscience.

[38]  Daniel M. Wolpert,et al.  Rhythmicity, randomness and synchrony in climbing fiber signals , 2005, Trends in Neurosciences.

[39]  M. Blumberg,et al.  Extraocular muscle activity, rapid eye movements and the development of active and quiet sleep , 2005, The European journal of neuroscience.

[40]  R. Ackerley,et al.  Pontine Maps Linking Somatosensory and Cerebellar Cortices Are in Register with Climbing Fiber Somatotopy , 2005, The Journal of Neuroscience.

[41]  M. Blumberg,et al.  The Neural Substrates of Infant Sleep in Rats , 2005, PLoS biology.

[42]  M. Blumberg,et al.  Thermal and nutritional modulation of sleep in infant rats. , 2005, Behavioral neuroscience.

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

[44]  G. Buzsáki,et al.  Early motor activity drives spindle bursts in the developing somatosensory cortex , 2004, Nature.

[45]  D. Puro,et al.  Maturation of evoked mossy fiber input to rat cerebellar Purkinje cells (II) , 1977, Experimental Brain Research.

[46]  D. Puro,et al.  Maturation of evoked climbing fiber input to rat cerebellar Purkinje cells (I.) , 1977, Experimental Brain Research.

[47]  E. Holst,et al.  Das Reafferenzprinzip , 2004, Naturwissenschaften.

[48]  P. Strata,et al.  A change in the pattern of activity affects the developmental regression of the purkinje cell polyinnervation by climbing fibers in the rat cerebellum , 2003, Neuroscience.

[49]  John H Freeman,et al.  Developmental changes in evoked Purkinje cell complex spike responses. , 2003, Journal of neurophysiology.

[50]  Jens Schouenborg,et al.  Spontaneous muscle twitches during sleep guide spinal self-organization , 2003, Nature.

[51]  M. Blumberg,et al.  Hippocampal Theta in the Newborn Rat Is Revealed under Conditions That Promote REM Sleep , 2003, The Journal of Neuroscience.

[52]  G. Buzsáki,et al.  Correlated Bursts of Activity in the Neonatal Hippocampus in Vivo , 2002, Science.

[53]  P. Andre,et al.  Modulation of Purkinje cell response to glutamate during the sleep–waking cycle , 2001, Neuroscience.

[54]  Huda Y. Zoghbi,et al.  Genetic regulation of cerebellar development , 2001, Nature Reviews Neuroscience.

[55]  M. Blumberg.  The Developmental Context of Thermal Homeostasis , 2001 .

[56]  Masahiko Watanabe,et al.  Critical Period for Activity-Dependent Synapse Elimination in Developing Cerebellum , 2000, The Journal of Neuroscience.

[57]  I. Feinberg,et al.  Schizophrenia – a disorder of the corollary discharge systems that integrate the motor systems of thought with the sensory systems of consciousness , 1999, British Journal of Psychiatry.

[58]  Michael J. O'Donovan.  The origin of spontaneous activity in developing networks of the vertebrate nervous system , 1999, Current Opinion in Neurobiology.

[59]  R. Wong,et al.  Retinal waves and visual system development. , 1999, Annual review of neuroscience.

[60]  D. Wolpert,et al.  Internal models in the cerebellum , 1998, Trends in Cognitive Sciences.

[61]  C. Shatz,et al.  Synaptic Activity and the Construction of Cortical Circuits , 1996, Science.

[62]  D. Tolbert,et al.  Chronic NMDA receptor blockade or muscimol inhibition of cerebellar cortical neuronal activity alters the development of spinocerebellar afferent topography. , 1994, Brain research. Developmental brain research.

[63]  J. Houk,et al.  Movement-related inputs to intermediate cerebellum of the monkey. , 1993, Journal of neurophysiology.

[64]  K. Maekawa,et al.  Transient direct connection of vestibular mossy fibers to the vestibulocerebellar Purkinje cells in early postnatal development of kittens , 1989, Neuroscience.

[65]  R. Llinás,et al.  The Functional Organization of the Olivo‐Cerebellar System as Examined by Multiple Purkinje Cell Recordings , 1989, The European journal of neuroscience.

[66]  Y. Prigent.  [Long term depression]. , 1989, Annales medico-psychologiques.

[67]  L. Maffei,et al.  Spontaneous impulse activity of rat retinal ganglion cells in prenatal life. , 1988, Science.

[68]  T. Ebner,et al.  Rhythmic discharge of climbing fibre afferents in response to natural peripheral stimuli in the cat. , 1984, The Journal of physiology.

[69]  C. Mason,et al.  Postnatal maturation of cerebellar mossy and climbing fibers: transient expression of dual features on single axons , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[70]  W. G. Hall,et al.  Suckling Isn't Feeding, or Is It? A Search for Developmental Continuities , 1983 .

[71]  M Mirmiran,et al.  Neuronal discharge patterns in the occipital cortex of developing rats during active and quiet sleep. , 1982, Brain research.

[72]  K. Lissák,et al.  Early postnatal development of wakefulness-sleep cycle and neuronal responsiveness: a multiunit activity study on freely moving newborn rat. , 1980, Electroencephalography and clinical neurophysiology.

[73]  L. Korányi,et al.  Multiunits in the mesencephalic reticular formation: ontogenetic development of wakefulness and sleep cycle in the rat. , 1980, Neuroscience letters.

[74]  V. Tam,et al.  EARLY POSTNATAL DEVELOPMENT OF WAKEFULNESS-SLEE P AND NEURONAL RESPONSIVENESS: A MULTIUNIT ACTIVITY STUDY ON FREELY MOVING NEWBORN RAT 1 , 1980 .

[75]  W. G. Hall,et al.  Appetitive learning in 1-day-old rat pups. , 1979, Science.

[76]  A. Gramsbergen.  The development of the EEG in the rat. , 1976, Developmental Psychobiology.

[77]  K. Sasaki,et al.  Electrophysiological study on the postnatal development of neuronal mechanisms in the rat cerebellar cortex , 1976, Brain Research.

[78]  Multiple firings by cat cerebellar Purkinje cells in sleep and waking. , 1974, Experimental neurology.

[79]  J. Altman,et al.  Postnatal development of the cerebellar cortex in the rat. I. The external germinal layer and the transitional molecular layer , 1972, The Journal of comparative neurology.

[80]  F. Crépel,et al.  Maturation of climbing fiber responses in the rat. , 1971, Brain research.

[81]  N. Mano,et al.  Changes of Simple and Complex Spike Activity of Cerebellar Purkinje Cells with Sleep and Waking , 1970, Science.

[82]  A Gramsbergen,et al.  The postnatal development of behavioral states in the rat. , 1970, Developmental psychobiology.

[83]  L. Astic,et al.  Ontogenesis of the states of sleep in rat, cat, and guinea pig during the first postnatal month. , 1970, Developmental psychobiology.

[84]  D. Woodward,et al.  Postnatal development of electrical and enzyme histochemical activity in Purkinje cells. , 1969, Experimental neurology.

[85]  R. Sperry.  Neural basis of the spontaneous optokinetic response produced by visual inversion. , 1950, Journal of comparative and physiological psychology.