Identifying Purkinje cells using only their spontaneous simple spike activity

SummaryCerebellar plasticity underlies motor learning. However, how the cerebellum operates to enable learned changes in motor output is largely unknown. We developed a sensory-driven adaptation protocol for reflexive whisker protraction and recorded Purkinje cell activity from crus 1 and 2 of awake mice. Before training, simple spikes of individual Purkinje cells correlated during reflexive protraction with the whisker position without lead or lag. After training, simple spikes and whisker protractions were both enhanced with the spiking activity now leading the behavioral response. Neuronal and behavior changes did not occur in two cell-specific mouse models with impaired long-term potentiation at parallel fiber to Purkinje cell synapses. Consistent with cerebellar plasticity rules, increased simple spike activity was prominent in cells with low complex spike response probability. Thus, potentiation at parallel fiber to Purkinje cell synapses may contribute to reflex adaptation and enable expression of cerebellar learning through increases in simple spike activity.Impact statementRomano et al. show that expression of cerebellar whisker learning can be mediated by increases in simple spike activity, depending on LTP induction at parallel fiber to Purkinje cell synapses.

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Anoctamin 2-chloride channels reduce simple spike activity and mediate inhibition at elevated calcium concentration in cerebellar Purkinje cells

PLoS ONE ◽

10.1371/journal.pone.0247801 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247801

Author(s):

Friederike Auer ◽

Eliana Franco Taveras ◽

Uli Klein ◽

Céline Kesenheimer ◽

Dana Fleischhauer ◽

...

Keyword(s):

Purkinje Cells ◽

Spike Activity ◽

Chloride Channels ◽

Cell Activity ◽

High Threshold ◽

Chloride Currents ◽

Simple Spike ◽

Cerebellar Purkinje Cells ◽

Inferior Olivary

Modulation of neuronal excitability is a prominent way of shaping the activity of neuronal networks. Recent studies highlight the role of calcium-activated chloride currents in this context, as they can both increase or decrease excitability. The calcium-activated chloride channel Anoctamin 2 (ANO2 alias TMEM16B) has been described in several regions of the mouse brain, including the olivo-cerebellar system. In inferior olivary neurons, ANO2 was proposed to increase excitability by facilitating the generation of high-threshold calcium spikes. An expression of ANO2 in cerebellar Purkinje cells was suggested, but its role in these neurons remains unclear. In the present study, we confirmed the expression of Ano2 mRNA in Purkinje cells and performed electrophysiological recordings to examine the influence of ANO2-chloride channels on the excitability of Purkinje cells by comparing wildtype mice to mice lacking ANO2. Recordings were performed in acute cerebellar slices of adult mice, which provided the possibility to study the role of ANO2 within the cerebellar cortex. Purkinje cells were uncoupled from climbing fiber input to assess specifically the effect of ANO2 channels on Purkinje cell activity. We identified an attenuating effect of ANO2-mediated chloride currents on the instantaneous simple spike activity both during strong current injections and during current injections close to the simple spike threshold. Moreover, we report a reduction of inhibitory currents from GABAergic interneurons upon depolarization, lasting for several seconds. Together with the role of ANO2-chloride channels in inferior olivary neurons, our data extend the evidence for a role of chloride-dependent modulation in the olivo-cerebellar system that might be important for proper cerebellum-dependent motor coordination and learning.

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Differential Purkinje cell simple spike activity and pausing behavior related to cerebellar modules

Journal of Neurophysiology ◽

10.1152/jn.00925.2014 ◽

2015 ◽

Vol 113 (7) ◽

pp. 2524-2536 ◽

Cited By ~ 17

Author(s):

Haibo Zhou ◽

Kai Voges ◽

Zhanmin Lin ◽

Chiheng Ju ◽

Martijn Schonewille

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Cerebellar Cortex ◽

Spike Activity ◽

Vestibular Nuclei ◽

Simple Spike ◽

Transverse Zone ◽

Cerebellar Modules ◽

Lower Temperature ◽

Cerebellar Purkinje Cells

The massive computational capacity of the cerebellar cortex is conveyed by Purkinje cells onto cerebellar and vestibular nuclei neurons through their GABAergic, inhibitory output. This implies that pauses in Purkinje cell simple spike activity are potentially instrumental in cerebellar information processing, but their occurrence and extent are still heavily debated. The cerebellar cortex, although often treated as such, is not homogeneous. Cerebellar modules with distinct anatomical connectivity and gene expression have been described, and Purkinje cells in these modules also differ in firing rate of simple and complex spikes. In this study we systematically correlate, in awake mice, the pausing in simple spike activity of Purkinje cells recorded throughout the entire cerebellum, with their location in terms of lobule, transverse zone, and zebrin-identified cerebellar module. A subset of Purkinje cells displayed long (>500-ms) pauses, but we found that their occurrence correlated with tissue damage and lower temperature. In contrast to long pauses, short pauses (<500 ms) and the shape of the interspike interval (ISI) distributions can differ between Purkinje cells of different lobules and cerebellar modules. In fact, the ISI distributions can differ both between and within populations of Purkinje cells with the same zebrin identity, and these differences are at least in part caused by differential synaptic inputs. Our results suggest that long pauses are rare but that there are differences related to shorter intersimple spike intervals between and within specific subsets of Purkinje cells, indicating a potential further segregation in the activity of cerebellar Purkinje cells.

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Changes in Simple Spike Activity of Some Purkinje Cells in the Oculomotor Vermis during Saccade Adaptation Are Appropriate to Participate in Motor Learning

Journal of Neuroscience ◽

10.1523/jneurosci.4953-09.2010 ◽

2010 ◽

Vol 30 (10) ◽

pp. 3715-3727 ◽

Cited By ~ 51

Author(s):

Y. Kojima ◽

R. Soetedjo ◽

A. F. Fuchs

Keyword(s):

Motor Learning ◽

Purkinje Cells ◽

Spike Activity ◽

Simple Spike ◽

Oculomotor Vermis ◽

Saccade Adaptation

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Barbiturate depresses simple spike activity of cerebellar Purkinje cells after climbing fiber input

Journal of Neurophysiology ◽

10.1152/jn.1993.69.4.1082 ◽

1993 ◽

Vol 69 (4) ◽

pp. 1082-1090 ◽

Cited By ~ 43

Author(s):

Y. Sato ◽

A. Miura ◽

H. Fushiki ◽

T. Kawasaki

Keyword(s):

Total Dose ◽

Purkinje Cells ◽

Spike Activity ◽

Climbing Fiber ◽

T Test ◽

Pentobarbital Sodium ◽

Simple Spike ◽

Before And After ◽

Cerebellar Purkinje Cells ◽

Decerebrate Cats

1. Some scientists reported that the simple spike (SS) activity was transiently depressed after climbing fiber input, but others reported that predominant population of Purkinje cells increased their SS activity after the complex spike (CS). In the present study, SS activity after spontaneous CS was compared before and after the administration of pentobarbital sodium and of ketamine in high decerebrate cats. 2. Frequencies of spontaneous CS and SS firing were reduced (P < 0.001, t test) after pentobarbital administration of a total dose of 20-30 mg/kg. 3. In the peri-CS time histogram, the SS activity during a post-CS period of 10-110 ms with respect to that during a pre-CS period of -100-0 ms was reduced (P < 0.001) after the pentobarbital administration from, on average, 132.4 to 81.9%. In contrast, the SS activity during a post-CS period of 110-210 ms remained unchanged (P > 0.2). 4. In the pre-CS time histogram constructed after the pentobarbital administration, there were no significant differences (P > 0.01) between the SS activity during a pre-CS period of -600 to -500 ms and that during each of other pre-CS periods, suggesting that the barbiturate had little effect on the SS activity preceding the CS. 5. Analysis of raster diagrams revealed the variability of individual SS activity after the CS.(ABSTRACT TRUNCATED AT 250 WORDS)

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Simple spike and complex spike activity of floccular Purkinje cells during the optokinetic reflex in mice lacking cerebellar long-term depression

European Journal of Neuroscience ◽

10.1111/j.0953-816x.2003.03173.x ◽

2004 ◽

Vol 19 (3) ◽

pp. 687-697 ◽

Cited By ~ 36

Author(s):

H. H. L. M. Goossens ◽

F. E. Hoebeek ◽

A. M. van Alphen ◽

J. van der Steen ◽

J. S. Stahl ◽

...

Keyword(s):

Purkinje Cells ◽

Spike Activity ◽

Long Term Depression ◽

Complex Spike ◽

Simple Spike ◽

Optokinetic Reflex

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Encoding of Movement Dynamics by Purkinje Cell Simple Spike Activity During Fast Arm Movements Under Resistive and Assistive Force Fields

Journal of Neurophysiology ◽

10.1152/jn.00206.2006 ◽

2007 ◽

Vol 97 (2) ◽

pp. 1588-1599 ◽

Cited By ~ 36

Author(s):

Kenji Yamamoto ◽

Mitsuo Kawato ◽

Shinya Kotosaka ◽

Shigeru Kitazawa

Keyword(s):

Force Field ◽

Purkinje Cells ◽

Spike Activity ◽

Force Fields ◽

Arm Movements ◽

Electromyographic Activity ◽

Simple Spike ◽

Movement Dynamics ◽

The Difference ◽

Intermediate Part

It is controversial whether simple-spike activity of cerebellar Purkinje cells during arm movements encodes movement kinematics like velocity or dynamics like muscle activities. To examine this issue, we trained monkeys to flex or extend the elbow by 45° in 400 ms under resistive and assistive force fields but without altering kinematics. During the task movements after training, simple-spike discharges were recorded in the intermediate part of the cerebellum in lobules V–VI, and electromyographic activity was recorded from arm muscles. Velocity profiles (kinematics) in the two force fields were almost identical to each other, whereas not only the electromyographic activities (dynamics) but also simple-spike activities in many Purkinje cells differed distinctly depending on the type of force field. Simple-spike activities encoded much larger mutual information with the type of force field than that with the residual small difference in the height of peak velocity. The difference in simple-spike activities averaged over the recorded Purkinje-cells increased ∼40 ms before the appearance of the difference in electromyographic activities between the two force fields, suggesting that the difference of simple-spike activities could be the origin of the difference of muscle activities. Simple-spike activity of many Purkinje cells correlated with electromyographic activity with a lead of ∼80 ms, and these neurons had little overlap with another group of neurons the simple-spike activity of which correlated with velocity profiles. These results show that simple-spike activity of at least a group of Purkinje cells in the intermediate part of cerebellar lobules V–VI encodes movement dynamics.

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