Using extracellular low frequency signals to improve the spike sorting of cerebellar complex spikes

BACKGROUND The challenge of spike sorting has been addressed by numerous electrophysiological studies. These methods tend to focus on the information conveyed by the high frequencies, but ignore the potentially informative signals at lower frequencies. Activation of Purkinje cells in the cerebellum by input from the climbing fibers results in a large amplitude dendritic spike concurrent with a high-frequency burst known as a complex spike. Due to the variability in the high-frequency component of complex spikes, previous methods have struggled to sort these complex spikes in an accurate and reliable way. However, complex spikes have a prominent extracellular low-frequency signal generated by the input from the climbing fibers, which can be exploited for complex spike sorting. NEW METHOD We exploited the low-frequency signal (20-400 Hz) to improve complex spike sorting by applying Principal Component Analysis (PCA). RESULTS AND COMPARISONS The low-frequency first PC achieves a better separation of the complex spikes from noise. The low-frequency data facilitate the detection of events entering into the analysis, and therefore can be harnessed to analyze the data with a larger signal to noise ratio. These advantages make this method more effective for complex spike sorting than methods restricted to the high-frequency signal (> 600 Hz). CONCLUSIONS Gathering low frequency data can improve spike sorting. This is illustrated for the case of complex spikes in the cerebellum. Our characterization of the dendritic low-frequency components of complex spikes can be applied elsewhere to gain insights into processing in the cerebellum.

[1]  J. Raymond,et al.  Timing Rules for Synaptic Plasticity Matched to Behavioral Function , 2016, Neuron.

[2]  J A Hobson,et al.  Spontaneous discharge rates of cat cerebellar Purkinje cells in sleep and waking. , 1972, Electroencephalography and clinical neurophysiology.

[3]  C. Koch,et al.  On the origin of the extracellular action potential waveform: A modeling study. , 2006, Journal of neurophysiology.

[4]  Shlomo Elias,et al.  Statistical Properties of Pauses of the High-Frequency Discharge Neurons in the External Segment of the Globus Pallidus , 2007, The Journal of Neuroscience.

[5]  Stephen G Lisberger,et al.  Reward Action in the Initiation of Smooth Pursuit Eye Movements , 2012, The Journal of Neuroscience.

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

[7]  R. Quian Quiroga,et al.  Unsupervised Spike Detection and Sorting with Wavelets and Superparamagnetic Clustering , 2004, Neural Computation.

[8]  Dimitrios A. Adamos,et al.  Performance evaluation of PCA-based spike sorting algorithms , 2008, Comput. Methods Programs Biomed..

[9]  Mati Joshua,et al.  Cerebellar climbing fibers encode expected reward size , 2019, bioRxiv.

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

[11]  J. Albus A Theory of Cerebellar Function , 1971 .

[12]  Mario Negrello,et al.  Duration of Purkinje cell complex spikes increases with their firing frequency , 2015, Front. Cell. Neurosci..

[13]  M. Häusser,et al.  The Origin of the Complex Spike in Cerebellar Purkinje Cells , 2008, The Journal of Neuroscience.

[14]  Masanobu Kano,et al.  Dendritic calcium signaling in cerebellar Purkinje cell , 2013, Neural Networks.

[15]  Mati Joshua,et al.  Quantifying the isolation quality of extracellularly recorded action potentials , 2007, Journal of Neuroscience Methods.

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

[17]  W. T. Thach,et al.  Purkinje cell activity during motor learning , 1977, Brain Research.

[18]  Germund Hesslow,et al.  Changes in complex spike activity during classical conditioning , 2014, Front. Neural Circuits.

[19]  B. Gähwiler,et al.  Climbing Fibre Responses in Olivo‐cerebellar Slice Cultures. II. Dynamics of Cytosolic Calcium in Purkinje Cells , 1991, The European journal of neuroscience.

[20]  M. Abeles,et al.  Multispike train analysis , 1977, Proceedings of the IEEE.

[21]  Jun Maruta,et al.  Identifying Purkinje cells using only their spontaneous simple spike activity , 2014, Journal of Neuroscience Methods.

[22]  Tatsuya Kimura,et al.  Cerebellar complex spikes encode both destinations and errors in arm movements , 1998, Nature.

[23]  C. Léna,et al.  Tetrode recordings in the cerebellar cortex , 2012, Journal of Physiology-Paris.

[24]  Bijan Pesaran,et al.  Investigating large-scale brain dynamics using field potential recordings: analysis and interpretation , 2018, Nature Neuroscience.

[25]  Jan Voogd,et al.  The anatomy of the cerebellum , 1998, Trends in Cognitive Sciences.

[26]  Arnd Roth,et al.  Initiation of simple and complex spikes in cerebellar Purkinje cells , 2010, The Journal of physiology.

[27]  Peter Thier,et al.  Using deep neural networks to detect complex spikes of cerebellar Purkinje Cells , 2019, bioRxiv.

[28]  Masao Ito,et al.  Climbing fibre induced depression of both mossy fibre responsiveness and glutamate sensitivity of cerebellar Purkinje cells , 1982, The Journal of physiology.

[29]  R. Llinás,et al.  Patterns of Spontaneous Purkinje Cell Complex Spike Activity in the Awake Rat , 1999, The Journal of Neuroscience.

[30]  John C. Eccles,et al.  The Climbing Fiber Input and its Excitation of Purkinje Cells , 1967 .

[31]  J. Eccles,et al.  The excitatory synaptic action of climbing fibres on the Purkinje cells of the cerebellum , 1966, The Journal of physiology.

[32]  H. Sompolinsky,et al.  Purkinje cells in awake behaving animals operate at the upstate membrane potential , 2006, Nature Neuroscience.

[33]  M S Lewicki,et al.  A review of methods for spike sorting: the detection and classification of neural action potentials. , 1998, Network.

[34]  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.

[35]  D. Marr A theory of cerebellar cortex , 1969, The Journal of physiology.