Signaling of Predictive and Feedback Information in Purkinje Cell 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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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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Congruence of spatial organization of tactile projections to granule cell and Purkinje cell layers of cerebellar hemispheres of the albino rat: vertical organization of cerebellar cortex

Journal of Neurophysiology ◽

10.1152/jn.1983.49.3.745 ◽

1983 ◽

Vol 49 (3) ◽

pp. 745-766 ◽

Cited By ~ 248

Author(s):

J. M. Bower ◽

D. C. Woolston

Keyword(s):

Purkinje Cell ◽

Cerebellar Cortex ◽

Body Surface ◽

Granule Cell ◽

Spike Activity ◽

Body Part ◽

Parallel Fibers ◽

Simple Spike ◽

Vertical Organization ◽

Stimulation Of

1. We compared the spatial pattern of shortest latency somatosensory (tactile) projections to the Purkinje cell (PC) layer and to the underlying granule cell (GC) layer in tactile areas of rat cerebellar cortex. Micro-mapping methods were used to sample single units in the PC layer and multiple units in the GC layer of both anesthetized and unanesthetized rats. Mechanical and electrical stimulation of the body surface were employed. Responsiveness of PCs to cutaneous stimulation was assessed by constructing histograms of simple spike activity and statistically comparing poststimulus activity to nonstimulated base-line PC activity. 2. We found that PCs respond to tactile stimulation with increases (7-10 ms) followed by decreases (8-15 ms) in simple spike activity. Increases in simple spike activity followed activation of the underlying GC layer by 1-4 ms, while decreases in simple spike activity were found 2-5 ms after GC layer activation. 3. PCs were found to have both excitatory and inhibitory receptive fields (RFs). Excitatory RFs were restricted to small areas of a single body part and for each PC were very similar or identical to the RFs of neurons in the immediately subjacent GC layer. Inhibitory PC RFs were larger, often containing more than one body part and for each PC, were only partially similar to the RFs of subjacent GCs. PC inhibitory RFs also often included body surfaces projecting to the nearby but not to the underlying GC layer. 4. Stimulation of a single peripheral locus resulted in small, distinct regions of PC layer excitation and inhibition. Areas of PC excitation overlie activated regions of the GC layer, while inhibited PCs overlie both activated and nonactivated GC regions. 5. We found PCs to be organized in groups or patches with respect to the specific body region that was capable of activating them (upper lip, lower lip, etc.). Adjacent patches of PCs often represented widely separated body parts. This pattern of PC layer activating RF projections was congruent with the pattern of excitatory RF projections to the underlying GC layer. 6. These results indicate that there is a vertical organization in GC-PC excitatory relations, while GC-induced PC inhibition is slightly more widely distributed. 7. Our finding that the patchlike activation of PCs is congruent with that of the underlying GC layer contrasts with the classical concept that PCs are activated by parallel fibers in a "beamlike" fashion from a patch of GCs. Thus, a reevaluation of the role of parallel fibers seems to us to be in order. 8. In conclusion, our results support the view that short-latency afferent tactile projections to both the GC and PC layers of cerebellar cortex are highly organized spatially. This specificity of body surface projections must be incorporated into modern views of the functional organization of cerebellar cortex.

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Current source density correlates of cerebellar Golgi and Purkinje cell responses to tactile input

Journal of Neurophysiology ◽

10.1152/jn.00317.2010 ◽

2011 ◽

Vol 105 (3) ◽

pp. 1327-1341 ◽

Cited By ~ 13

Author(s):

Koen Tahon ◽

Mike Wijnants ◽

Erik De Schutter ◽

Reinoud Maex

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Spike Activity ◽

Granular Layer ◽

Current Source ◽

Current Source Density ◽

Golgi Cell ◽

Golgi Cells ◽

Source Density ◽

Simple Spike

The overall circuitry of the cerebellar cortex has been known for over a century, but the function of many synaptic connections remains poorly characterized in vivo. We used a one-dimensional multielectrode probe to estimate the current source density (CSD) of Crus IIa in response to perioral tactile stimuli in anesthetized rats and to correlate current sinks and sources to changes in the spike rate of corecorded Golgi and Purkinje cells. The punctate stimuli evoked two distinct early waves of excitation (at <10 and ∼20 ms) associated with current sinks in the granular layer. The second wave was putatively of corticopontine origin, and its associated sink was located higher in the granular layer than the first trigeminal sink. The distinctive patterns of granular-layer sinks correlated with the spike responses of corecorded Golgi cells. In general, Golgi cell spike responses could be linearly reconstructed from the CSD profile. A dip in simple-spike activity of coregistered Purkinje cells correlated with a current source deep in the molecular layer, probably generated by basket cell synapses, interspersed between sparse early sinks presumably generated by synapses from granule cells. The late (>30 ms) enhancement of simple-spike activity in Purkinje cells was characterized by the absence of simultaneous sinks in the granular layer and by the suppression of corecorded Golgi cell activity, pointing at inhibition of Golgi cells by Purkinje axon collaterals as a likely mechanism of late Purkinje cell excitation.

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A Purkinje cell model that simulates complex spikes

10.1101/2020.05.18.102236 ◽

2020 ◽

Author(s):

Amelia Burroughs ◽

Nadia L. Cerminara ◽

Richard Apps ◽

Conor Houghton

Keyword(s):

Action Potential ◽

Purkinje Cell ◽

Spike Activity ◽

Cell Model ◽

Compartment Model ◽

Complex Spike ◽

Simple Spike ◽

Lower Amplitude ◽

Complex Spikes

AbstractPurkinje cells are the principal neurons of the cerebellar cortex. One of their distinguishing features is that they fire two distinct types of action potential, called simple and complex spikes, which interact with one another. Simple spikes are stereotypical action potentials that are elicited at high, but variable, rates (0 – 100 Hz) and have a consistent waveform. Complex spikes are composed of an initial action potential followed by a burst of lower amplitude spikelets. Complex spikes occur at comparatively low rates (~ 1 Hz) and have a variable waveform. Although they are critical to cerebellar operation a simple model that describes the complex spike waveform is lacking. Here, a novel single-compartment model of Purkinje cell electrodynamics is presented. The simpler version of this model, with two active conductances and a leak channel, can simulate the features typical of complex spikes recorded in vitro. If calcium dynamics are also included, the model can capture the pause in simple spike activity that occurs after complex spike events. Together, these models provide an insight into the mechanisms behind complex spike spikelet generation, waveform variability and their interactions with simple spike activity.

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Potentiation of cerebellar Purkinje cells facilitates whisker reflex adaptation through increased simple spike activity

eLife ◽

10.7554/elife.38852 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 21

Author(s):

Vincenzo Romano ◽

Licia De Propris ◽

Laurens WJ Bosman ◽

Pascal Warnaar ◽

Michiel M ten Brinke ◽

...

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Spike Activity ◽

Cell Activity ◽

Response Probability ◽

Long Term Potentiation ◽

Parallel Fiber ◽

Spike Response ◽

Simple Spike ◽

Cerebellar Plasticity

Cerebellar 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 behavioral responses. Neuronal and behavioral changes did not occur in two cell-specific mouse models with impaired long-term potentiation at their 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.

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Functional convergence of autonomic and sensorimotor processing in the lateral cerebellum

10.1101/683573 ◽

2019 ◽

Author(s):

Vincenzo Romano ◽

Aoibhinn L. Reddington ◽

Silvia Cazzanelli ◽

Mario Negrello ◽

Laurens W.J. Bosman ◽

...

Keyword(s):

Purkinje Cell ◽

Ampa Receptors ◽

Spike Activity ◽

Cell Activity ◽

Respiratory Control ◽

Dependent Manner ◽

Sensorimotor Processing ◽

Simple Spike ◽

Whisker Stimulation ◽

The Impact

The cerebellum is involved in control of voluntary and autonomic rhythmic behaviors, yet it is largely unclear to what extent it coordinates these in a concerted action. Here, we studied Purkinje cell activity during unperturbed and perturbed respiration in cerebellar lobules simplex, crus 1 and 2. During unperturbed (eupneic) respiration complex spike and simple spike activity encoded respiratory activity, the timing of which corresponded with ongoing sensorimotor feedback. Instead, upon whisker stimulation mice concomitantly accelerated their simple spike activity and inspiration in a phase-dependent manner. Moreover, the accelerating impact of whisker stimulation on respiration could be mimicked by optogenetic stimulation of Purkinje cells and prevented by cell-specific genetic modification of their AMPA receptors that hampered increases in simple spike firing. Thus, the impact of Purkinje cell activity on respiratory control is context- and phase-dependent, suggesting a coordinating role for the cerebellar hemispheres in aligning autonomic and sensorimotor behaviors.

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