scholarly journals Calcium imaging reveals coordinated simple spike pauses in populations of Cerebellar Purkinje cells

2016 ◽  
Author(s):  
Jorge E. Ramirez ◽  
Brandon M. Stell
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Calcium Imaging ◽  
Spatial Organization ◽  
Cell Activity ◽  
Cerebellar Nuclei ◽  
Deep Cerebellar Nuclei ◽  
Firing Rates ◽  
Simple Spike ◽  
Cerebellar Purkinje Cells

The brain’s control of movement is thought to involve coordinated activity between cerebellar Purkinje cells. The results reported here demonstrate that somatic Ca2+ imaging is a faithful reporter of Na+-dependent “simple spike” pauses and enables us to optically record changes in firing rates in populations of Purkinje cells. This simultaneous calcium imaging of populations of Purkinje cells reveals a striking spatial organization of pauses in Purkinje cell activity between neighboring cells. The source of this organization is shown to be the presynaptic GABAergic network and blocking GABAARs abolishes the synchrony. These data suggest that presynaptic interneurons synchronize (in)activity between neighboring Purkinje cells and thereby maximize their effect on downstream targets in the deep cerebellar nuclei.

scholarly journals Disrupted Calcium Signaling in Animal Models of Human Spinocerebellar Ataxia (SCA)

2019 ◽  
Vol 21 (1) ◽  
pp. 216 ◽  
Author(s):  
Francesca Prestori ◽  
Francesco Moccia ◽  
Egidio D’Angelo
Keyword(s):  
Animal Models ◽  
Purkinje Cell ◽  
Calcium Signaling ◽  
Purkinje Cells ◽  
Motor Coordination ◽  
Cerebellar Atrophy ◽  
Cerebellar Nuclei ◽  
Spinocerebellar Ataxias ◽  
Cell Degeneration ◽  
Cerebellar Purkinje Cells

Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of more than 40 autosomal-dominant genetic and neurodegenerative diseases characterized by loss of balance and motor coordination due to dysfunction of the cerebellum and its efferent connections. Despite a well-described clinical and pathological phenotype, the molecular and cellular events that underlie neurodegeneration are still poorly undaerstood. Emerging research suggests that mutations in SCA genes cause disruptions in multiple cellular pathways but the characteristic SCA pathogenesis does not begin until calcium signaling pathways are disrupted in cerebellar Purkinje cells. Ca2+ signaling in Purkinje cells is important for normal cellular function as these neurons express a variety of Ca2+ channels, Ca2+-dependent kinases and phosphatases, and Ca2+-binding proteins to tightly maintain Ca2+ homeostasis and regulate physiological Ca2+-dependent processes. Abnormal Ca2+ levels can activate toxic cascades leading to characteristic death of Purkinje cells, cerebellar atrophy, and ataxia that occur in many SCAs. The output of the cerebellar cortex is conveyed to the deep cerebellar nuclei (DCN) by Purkinje cells via inhibitory signals; thus, Purkinje cell dysfunction or degeneration would partially or completely impair the cerebellar output in SCAs. In the absence of the inhibitory signal emanating from Purkinje cells, DCN will become more excitable, thereby affecting the motor areas receiving DCN input and resulting in uncoordinated movements. An outstanding advantage in studying the pathogenesis of SCAs is represented by the availability of a large number of animal models which mimic the phenotype observed in humans. By mainly focusing on mouse models displaying mutations or deletions in genes which encode for Ca2+ signaling-related proteins, in this review we will discuss the several pathogenic mechanisms related to deranged Ca2+ homeostasis that leads to significant Purkinje cell degeneration and dysfunction.

Dynamic Synchronization of Purkinje Cell Simple Spikes

2006 ◽  
Vol 96 (6) ◽  
pp. 3485-3491 ◽  
Author(s):  
Soon-Lim Shin ◽  
Erik De Schutter
Keyword(s):  
Purkinje Cell ◽  
Firing Rate ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Cerebellar Nuclei ◽  
Temporal Coding ◽  
Sharp Peak ◽  
Deep Cerebellar Nuclei

Purkinje cells (PCs) integrate all computations performed in the cerebellar cortex to inhibit neurons in the deep cerebellar nuclei (DCN). Simple spikes recorded in vivo from pairs of PCs separated by <100 μm are known to be synchronized with a sharp peak riding on a broad peak, but the significance of this finding is unclear. We show that the sharp peak consists exclusively of simple spikes associated with pauses in firing. The broader, less precise peak was caused by firing-rate co-modulation of faster firing spikes. About 13% of all pauses were synchronized, and these pauses had a median duration of 20 ms. As in vitro studies have reported that synchronous pauses can reliably trigger spikes in DCN neurons, we suggest that the subgroup of spikes causing the sharp peak is important for precise temporal coding in the cerebellum.

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

2018 ◽  
Author(s):  
Vincenzo Romano ◽  
Licia De Propris ◽  
Laurens W.J. 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

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.

scholarly journals Purkinje Cell Representations of Behavior: Diary of a Busy Neuron

2018 ◽  
Vol 25 (3) ◽  
pp. 241-257 ◽  
Author(s):  
Laurentiu S. Popa ◽  
Martha L. Streng ◽  
Timothy J. Ebner
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Motor Behavior ◽  
Cell Activity ◽  
Computational Framework ◽  
Simple Spike ◽  
Cerebellar Function ◽  
Performance Error ◽  
And Performance ◽  
High Degree

Fundamental for understanding cerebellar function is determining the representations in Purkinje cell activity, the sole output of the cerebellar cortex. Up to the present, the most accurate descriptions of the information encoded by Purkinje cells were obtained in the context of motor behavior and reveal a high degree of heterogeneity of kinematic and performance error signals encoded. The most productive framework for organizing Purkinje cell firing representations is provided by the forward internal model hypothesis. Direct tests of this hypothesis show that individual Purkinje cells encode two different forward models simultaneously, one for effector kinematics and one for task performance. Newer results demonstrate that the timing of simple spike encoding of motor parameters spans an extend interval of up to ±2 seconds. Furthermore, complex spike discharge is not limited to signaling errors, can be predictive, and dynamically controls the information in the simple spike firing to meet the demands of upcoming behavior. These rich, diverse, and changing representations highlight the integrative aspects of cerebellar function and offer the opportunity to generalize the cerebellar computational framework over both motor and non-motor domains.

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

PLoS ONE ◽  
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.

scholarly journals Cerebellar Purkinje cell activity modulates aggressive behavior

2020 ◽  
Author(s):  
Skyler L. Jackman ◽  
Christopher H. Chen ◽  
Heather L. Offermann ◽  
Iain R. Drew ◽  
Bailey M. Harrison ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Aggressive Behavior ◽  
Purkinje Cells ◽  
Motor Function ◽  
Cell Activity ◽  
Cerebellar Vermis ◽  
Cognitive Behaviors ◽  
Affective Behaviors ◽  
Cerebellar Purkinje Cells ◽  
The Impact

AbstractAlthough the cerebellum is traditionally associated with balance and motor function, it also plays wider roles in affective and cognitive behaviors. Evidence suggests that the cerebellar vermis may regulate aggressive behavior, though the cerebellar circuits and patterns of activity that influence aggression remain unclear. We used optogenetic methods to bidirectionally modulate the activity of spatially-delineated cerebellar Purkinje cells to evaluate the impact on aggression in mice. Increasing Purkinje cell activity in the vermis significantly reduced the frequency of attacks in a resident-intruder assay. Reduced aggression was not a consequence of impaired motor function, because optogenetic stimulation did not alter motor performance. In complementary experiments, optogenetic inhibition of Purkinje cells in the vermis increased the frequency of attacks. These results establish Purkinje cell activity in the cerebellar vermis regulates aggression, and further support the importance of the cerebellum in driving affective behaviors that could contribute to neurological disorders.

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

2015 ◽  
Vol 113 (7) ◽  
pp. 2524-2536 ◽  
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.

scholarly journals In vivo analysis of Purkinje cell firing properties during postnatal mouse development

2015 ◽  
Vol 113 (2) ◽  
pp. 578-591 ◽  
Author(s):  
Marife Arancillo ◽  
Joshua J. White ◽  
Tao Lin ◽  
Trace L. Stay ◽  
Roy V. Sillitoe
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Motor Behavior ◽  
Developmental Trajectories ◽  
Cell Activity ◽  
Mouse Development ◽  
Complex Spike ◽  
Simple Spike ◽  
Spike Firing

Purkinje cell activity is essential for controlling motor behavior. During motor behavior Purkinje cells fire two types of action potentials: simple spikes that are generated intrinsically and complex spikes that are induced by climbing fiber inputs. Although the functions of these spikes are becoming clear, how they are established is still poorly understood. Here, we used in vivo electrophysiology approaches conducted in anesthetized and awake mice to record Purkinje cell activity starting from the second postnatal week of development through to adulthood. We found that the rate of complex spike firing increases sharply at 3 wk of age whereas the rate of simple spike firing gradually increases until 4 wk of age. We also found that compared with adult, the pattern of simple spike firing during development is more irregular as the cells tend to fire in bursts that are interrupted by long pauses. The regularity in simple spike firing only reached maturity at 4 wk of age. In contrast, the adult complex spike pattern was already evident by the second week of life, remaining consistent across all ages. Analyses of Purkinje cells in alert behaving mice suggested that the adult patterns are attained more than a week after the completion of key morphogenetic processes such as migration, lamination, and foliation. Purkinje cell activity is therefore dynamically sculpted throughout postnatal development, traversing several critical events that are required for circuit formation. Overall, we show that simple spike and complex spike firing develop with unique developmental trajectories.

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