Heterogeneity of Purkinje cell simple spike–complex spike interactions: zebrin‐ and non‐zebrin‐related variations

Cerebellar Purkinje cells (PCs) generate two types of action potentials, simple and complex spikes. Although they are generated by distinct mechanisms, interactions between the two spike types exist. Zebrin staining produces alternating positive and negative stripes of PCs across most of the cerebellar cortex. Thus, here we compared simple spike–complex spike interactions both within and across zebrin populations. Simple spike activity undergoes a complex modulation preceding and following a complex spike. The amplitudes of the pre‐ and post‐complex spike modulation phases were correlated across PCs. On average, the modulation was larger for PCs in zebrin positive regions. Correlations between aspects of the complex spike waveform and simple spike activity were found, some of which varied between zebrin positive and negative PCs. The implications of the results are discussed with regard to hypotheses that complex spikes are triggered by rises in simple spike activity for either motor learning or homeostatic functions.

[1]  T. Ebner,et al.  The changes in Purkinje cell simple spike activity following spontaneous climbing fiber inputs , 1982, Brain Research.

[2]  I. Kanazawa,et al.  Complex-spike activity of cerebellar Purkinje cells related to wrist tracking movement in monkey. , 1986, Journal of neurophysiology.

[3]  Zhanmin Lin,et al.  Cerebellar modules operate at different frequencies , 2014, eLife.

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

[5]  H. Sompolinsky,et al.  Bistability of cerebellar Purkinje cells modulated by sensory stimulation , 2005, Nature Neuroscience.

[6]  J. Simpson,et al.  Discharges in Purkinje cell axons during climbing fiber activation. , 1971, Brain research.

[7]  Andrew K. Wise,et al.  Systematic Regional Variations in Purkinje Cell Spiking Patterns , 2014, PloS one.

[8]  Zayd M. Khaliq,et al.  Axonal Propagation of Simple and Complex Spikes in Cerebellar Purkinje Neurons , 2005, The Journal of Neuroscience.

[9]  C. Hansel,et al.  Purkinje Cell NMDA Receptors Assume a Key Role in Synaptic Gain Control in the Mature Cerebellum , 2010, The Journal of Neuroscience.

[10]  Martin Paukert,et al.  Zones of Enhanced Glutamate Release from Climbing Fibers in the Mammalian Cerebellum , 2010, The Journal of Neuroscience.

[11]  R. Hawkes Purkinje cell stripes and long-term depression at the parallel fiber-Purkinje cell synapse , 2014, Front. Syst. Neurosci..

[12]  M. Ito,et al.  Cerebellar long-term depression: characterization, signal transduction, and functional roles. , 2001, Physiological reviews.

[13]  E. J. Lang,et al.  Relationship of complex spike synchrony bands and climbing fiber projection determined by reference to aldolase C compartments in crus IIa of the rat cerebellar cortex , 2007, The Journal of comparative neurology.

[14]  M. Häusser,et al.  Determinants of Action Potential Propagation in Cerebellar Purkinje Cell Axons , 2005, The Journal of Neuroscience.

[15]  Zhanmin Lin,et al.  Differential Purkinje cell simple spike activity and pausing behavior related to cerebellar modules. , 2015, Journal of neurophysiology.

[16]  M. Häusser,et al.  Encoding of Oscillations by Axonal Bursts in Inferior Olive Neurons , 2009, Neuron.

[17]  Masanobu Kano,et al.  Presynaptic origin of paired‐pulse depression at climbing fibre‐Purkinje cell synapses in the rat cerebellum , 1998, The Journal of physiology.

[18]  Gang Chen,et al.  Cerebellar Cortical Molecular Layer Inhibition Is Organized in Parasagittal Zones , 2006, The Journal of Neuroscience.

[19]  N. H. Sabah,et al.  The inhibitory effect of climbing fiber activation on cerebellar purkinje cells. , 1970, Brain research.

[20]  T. Ebner,et al.  Increased responsiveness of Purkinje cells associated with climbing fiber inputs to neighboring neurons. , 1983, Journal of neurophysiology.

[21]  Riccardo Zucca,et al.  Number of Spikes in Climbing Fibers Determines the Direction of Cerebellar Learning , 2013, The Journal of Neuroscience.

[22]  F. Rubia,et al.  Inhibition of cerebellar Purkinje cells by climbing fiber input , 2004, Pflügers Archiv.

[23]  Javier F. Medina,et al.  Beyond “all-or-nothing” climbing fibers: graded representation of teaching signals in Purkinje cells , 2013, Front. Neural Circuits.

[24]  C. D. De Zeeuw,et al.  Motor Learning and the Cerebellum. , 2015, Cold Spring Harbor perspectives in biology.

[25]  W. T. Thach,et al.  Simple spike activity predicts occurrence of complex spikes in cerebellar Purkinje cells , 1998, Nature Neuroscience.

[26]  M. Barrot,et al.  Clusters of cerebellar Purkinje cells control their afferent climbing fiber discharge , 2013, Proceedings of the National Academy of Sciences.

[27]  Yan Yang,et al.  Duration of complex-spikes grades Purkinje cell plasticity and cerebellar motor learning , 2014, Nature.

[28]  D. H. Paul,et al.  Spontaneous activity of cerebellar Purkinje cells and their responses to impulses in climbing fibres , 1971, The Journal of physiology.

[29]  R Llinás,et al.  Interaction experiments on the responses evoked in Purkinje cells by climbing fibres , 1966, The Journal of physiology.

[30]  T. Ebner,et al.  Temporal patterning in simple spike discharge of Purkinje cells and its relationship to climbing fiber activity. , 1981, Journal of neurophysiology.

[31]  Mitsuo Kawato,et al.  The Roles of the Olivocerebellar Pathway in Motor Learning and Motor Control. A Consensus Paper , 2017, The Cerebellum.

[32]  E. J. Lang,et al.  Organization of Olivocerebellar Activity in the Absence of Excitatory Glutamatergic Input , 2001, The Journal of Neuroscience.

[33]  Andrew K. Wise,et al.  The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes , 2016, The Journal of physiology.

[34]  P. Strata,et al.  The inhibitory effect of the olivocerebellar input on the cerebellar Purkinje cells in the rat † , 1982, The Journal of physiology.

[35]  C. Levenes,et al.  NMDA Receptor Contribution to the Climbing Fiber Response in the Adult Mouse Purkinje Cell , 2007, The Journal of Neuroscience.

[36]  C. Bell,et al.  Discharge properties of Purkinje cells recorded on single and double microelectrodes. , 1969, Journal of Neurophysiology.

[37]  J. Desclin,et al.  The olivocerebellar system. I. Delayed and slow inhibitory effects: An overlooked salient feature of cerebellar climbing fibers , 1980, Brain Research.

[38]  T. Kawasaki,et al.  Short-term modulation of cerebellar Purkinje cell activity after spontaneous climbing fiber input. , 1992, Journal of neurophysiology.

[39]  Dilwyn E Marple-Horvat,et al.  Mechanisms of synchronous activity in cerebellar Purkinje cells , 2010, The Journal of physiology.

[40]  G. Hesslow,et al.  The secondary spikes of climbing fibre responses recorded from Purkinje cell somata in cat cerebellum. , 1986, The Journal of physiology.

[41]  T. Ebner,et al.  Increase in Purkinje cell gain associated with naturally activated climbing fiber input. , 1983, Journal of neurophysiology.

[42]  N. Donegan,et al.  A model of Pavlovian eyelid conditioning based on the synaptic organization of the cerebellum. , 1997, Learning & memory.

[43]  J. Rawson,et al.  Suppression of simple spike discharges of cerebellar Purkinje cells by impulses in climbing fibre afferents , 1981, Neuroscience Letters.

[44]  Timothy A. Blenkinsop,et al.  Synaptic Action of the Olivocerebellar System on Cerebellar Nuclear Spike Activity , 2011, The Journal of Neuroscience.

[45]  P. Gilbert Simple spike frequency and the number of secondary spikes in the complex spike of the cerebellar Purkinje cell , 1976, Brain Research.

[46]  G. Hesslow,et al.  The secondary spikes of climbing fibre responses recorded from Purkinje cell axons in cat cerebellum. , 1986, The Journal of physiology.

[47]  E. J. Lang,et al.  Local Changes in the Excitability of the Cerebellar Cortex Produce Spatially Restricted Changes in Complex Spike Synchrony , 2009, The Journal of Neuroscience.

[48]  Timothy A. Blenkinsop,et al.  Modulation of Purkinje cell complex spike waveform by synchrony levels in the olivocerebellar system , 2014, Front. Syst. Neurosci..

[49]  D. Robinson,et al.  Effects of electrical stimulation and reversible lesions of the olivocerebellar pathway on Purkinje cell activity in the flocculus of the cat , 1985, Brain Research.

[50]  Timothy A. Blenkinsop,et al.  Control of Cerebellar Nuclear Cells: A Direct Role for Complex Spikes? , 2011, The Cerebellum.

[51]  C. G. Phillips,et al.  Excitatory and inhibitory processes acting upon individual Purkinje cells of the cerebellum in cats , 1956, The Journal of physiology.

[52]  Germund Hesslow,et al.  Cerebellar control of the inferior olive , 2008, The Cerebellum.

[53]  J. Bloedel,et al.  Action of climbing fibers in cerebellar cortex of the cat. , 1971, Journal of neurophysiology.

[54]  T. Ebner,et al.  Role of climbing fiber afferent input in determining responsiveness of Purkinje cells to mossy fiber inputs. , 1981, Journal of neurophysiology.

[55]  J. Rawson,et al.  Evidence that Climbing Fibers Control an Intrinsic Spike Generator in Cerebellar Purkinje Cells , 2004, The Journal of Neuroscience.

[56]  W. T. Thach,et al.  Nonclock behavior of inferior olive neurons: interspike interval of Purkinje cell complex spike discharge in the awake behaving monkey is random. , 1995, Journal of neurophysiology.

[57]  F. Tempia,et al.  On the Purkinje cell activity increase induced by suppression of inferior olive activity , 2004, Experimental Brain Research.