scholarly journals Motor context dominates output from purkinje cell functional regions during reflexive visuomotor behaviours

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Laura D Knogler ◽  
Andreas M Kist ◽  
Ruben Portugues
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Cell Activity ◽  
Behavioral Repertoire ◽  
Sensory Stimuli ◽  
Larval Zebrafish ◽  
Functional Regions ◽  
Electrophysiological Recordings ◽  
Motor Signal ◽  
Motor Actions

The cerebellum integrates sensory stimuli and motor actions to enable smooth coordination and motor learning. Here we harness the innate behavioral repertoire of the larval zebrafish to characterize the spatiotemporal dynamics of feature coding across the entire Purkinje cell population during visual stimuli and the reflexive behaviors that they elicit. Population imaging reveals three spatially-clustered regions of Purkinje cell activity along the rostrocaudal axis. Complementary single-cell electrophysiological recordings assign these Purkinje cells to one of three functional phenotypes that encode a specific visual, and not motor, signal via complex spikes. In contrast, simple spike output of most Purkinje cells is strongly driven by motor-related tail and eye signals. Interactions between complex and simple spikes show heterogeneous modulation patterns across different Purkinje cells, which become temporally restricted during swimming episodes. Our findings reveal how sensorimotor information is encoded by individual Purkinje cells and organized into behavioral modules across the entire cerebellum.

scholarly journals Motor context dominates output from Purkinje cell functional regions during reflexive visuomotor behaviours

2018 ◽  
Author(s):  
Laura D. Knogler ◽  
Andreas M. Kist ◽  
Ruben Portugues
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Cell Activity ◽  
Behavioral Repertoire ◽  
Sensory Stimuli ◽  
Larval Zebrafish ◽  
Functional Regions ◽  
Electrophysiological Recordings ◽  
Motor Signal ◽  
Motor Actions

SUMMARYThe cerebellum integrates sensory stimuli and motor actions to enable smooth coordination and motor learning. Here we harness the innate behavioral repertoire of the larval zebrafish to characterize the spatiotemporal dynamics of feature coding across the entire Purkinje cell population during visual stimuli and the reflexive behaviors that they elicit. Population imaging reveals three spatially-clustered regions of Purkinje cell activity along the rostrocaudal axis. Complementary single-cell electrophysiological recordings assign these Purkinje cells to one of three functional phenotypes that encode a specific visual, and not motor, signal via complex spikes. In contrast, simple spike output of most Purkinje cells is strongly driven by motor-related tail and eye signals. Interactions between complex and simple spikes show heterogeneous modulation patterns across different Purkinje cells, which become temporally restricted during swimming episodes. Our findings reveal how sensorimotor information is encoded by individual Purkinje cells and organized into behavioral modules across the entire cerebellum.

scholarly journals VIP interneurons in mouse whisker S1 exhibit sensory and action-related signals during goal-directed behavior

2021 ◽  
Author(s):  
Deepa L Ramamurthy ◽  
Andrew Chen ◽  
Patrick C Huang ◽  
Priyanka Bharghavan ◽  
Gayathri Krishna ◽  
...  
Keyword(s):  
Cell Activity ◽  
Inhibitory Neuron ◽  
Sensory Cortex ◽  
Related Activity ◽  
Sensory Stimuli ◽  
State Dependent ◽  
Sensory Responses ◽  
Motor Actions ◽  
First Time ◽  
Goal Directed Behavior

Vasoactive intestinal peptide-expressing (VIP) interneurons, which constitute 10-15% of the cortical inhibitory neuron population, have emerged as an important cell type for regulating excitatory cell activity based on behavioral state. VIP cells in sensory cortex are potently engaged by neuromodulatory and motor inputs during active exploratory behaviors like locomotion and whisking, which in turn promote pyramidal cell firing via disinhibition. Such state-dependent modulation of activity by VIP cells in sensory cortex has been studied widely in recent years. However, the function of VIP cells during goal-directed behavior is less well understood. It is not clear how task-related events like sensory stimuli, motor actions, or reward activate VIP cells in sensory cortex since there is often temporal overlap in the occurrence of these events. We developed a Go/NoGo whisker touch detection task which incorporates a post-stimulus delay period to separate sensory-driven activity from action- or reward-related activity during behavior. We used 2-photon calcium imaging to measure task-related signals of L2/3 VIP neurons in S1 of behaving mice. We report for the first time that VIP cells in mouse whisker S1 are activated by both whisker stimuli and goal-directed licking. Whisker- and lick-related signals were spatially organized in relation to anatomical columns in S1. Sensory responses of VIP cells were tuned to specific whiskers, whether or not they also displayed lick-related activity.

scholarly journals Cerebellar neuronal dysfunction accompanies early motor symptoms in Spinocerebellar Ataxia Type 3 and is partially alleviated upon chronic citalopram treatment

2021 ◽  
Author(s):  
KJ Palarz ◽  
A Neves-Carvalho ◽  
S Duarte-Silva ◽  
P Maciel ◽  
K Khodakhah
Keyword(s):  
Mouse Model ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Spinocerebellar Ataxia ◽  
Cell Activity ◽  
Spinocerebellar Ataxia Type ◽  
Neuronal Dysfunction ◽  
Spinocerebellar Ataxia Type 3 ◽  
Cell Dysfunction ◽  
Type 3

ABSTRACTSpinocerebellar ataxia type 3 (SCA3) is an adult-onset, progressive ataxia with no current disease modifying treatments. SCA3 patients have mild degeneration of the cerebellum, a brain area involved in motor coordination and maintenance of balance, as well as of the brainstem, of the spinal cord and of other movement-related subcortical areas. However, both SCA3 patients and SCA3 mouse models present clinical symptoms before any gross pathology is detectable, which suggests neuronal dysfunction precedes neurodegeneration, and opens an opportunity for therapeutic intervention. Such observations also raise the question of what triggers these abnormal motor phenotypes. Purkinje cells are the major computational unit within the cerebellum and are responsible for facilitating coordinated movements. Abnormal Purkinje cell activity is sufficient to cause ataxia. In this study, we show that the CMVMJD135 mouse model of SCA3 has dysfunctional deep cerebellar nuclei and Purkinje cells. Both cell types have increased irregularity as measured by inter-spike interval coefficient of variation. Purkinje cell dysfunction is likely a combination of intrinsic and extrinsic (synaptic) dysfunction. Interestingly, Citalopram, a selective serotonin reuptake inhibitor previously shown to alleviate disease in CMVMJD135 mice, also improved cerebellar neuron function in the CMVMJD135 mouse model. Specifically, we found that Purkinje cell dysfunction when synaptic transmission is intact was alleviated with citalopram treatment, however, intrinsic Purkinje cell dysfunction was not alleviated. Altogether, our findings suggest that cerebellar neuronal dysfunction contributes to the onset of SCA3 motor dysfunction and that citalopram, while effective at alleviating the motor phenotype, does not restore Purkinje cell intrinsic activity in SCA3. A novel therapeutic approach that combines citalopram with another therapeutic that targets this intrinsic dysfunction in a complementary manner might further reduce disease burden in SCA3.

scholarly journals Responses of cerebellar Purkinje cells during fictive optomotor behavior in larval zebrafish

2016 ◽  
Vol 116 (5) ◽  
pp. 2067-2080 ◽  
Author(s):  
Karina Scalise ◽  
Takashi Shimizu ◽  
Masahiko Hibi ◽  
Nathaniel B. Sawtell
Keyword(s):  
Purkinje Cells ◽  
Climbing Fiber ◽  
Visual Responses ◽  
Optomotor Response ◽  
General Role ◽  
Larval Stages ◽  
Larval Zebrafish ◽  
Electrophysiological Recordings ◽  
Cerebellar Purkinje Cells ◽  
Climbing Fiber Responses

Although most studies of the cerebellum have been conducted in mammals, cerebellar circuitry is highly conserved across vertebrates, suggesting that studies of simpler systems may be useful for understanding cerebellar function. The larval zebrafish is particularly promising in this regard because of its accessibility to optical monitoring and manipulations of neural activity. Although several studies suggest that the cerebellum plays a role in behavior at larval stages, little is known about the signals conveyed by particular classes of cerebellar neurons. Here we use electrophysiological recordings to characterize subthreshold, simple spike, and climbing fiber responses in larval zebrafish Purkinje cells in the context of the fictive optomotor response (OMR)—a paradigm in which fish adjust motor output to stabilize their virtual position relative to a visual stimulus. Although visual responses were prominent in Purkinje cells, they lacked the direction or velocity sensitivity that would be expected for controlling the OMR. On the other hand, Purkinje cells exhibited strong responses during fictive swim bouts. Temporal characteristics of these responses are suggestive of a general role for the larval zebrafish cerebellum in controlling swimming. Climbing fibers encoded both visual and motor signals but did not appear to encode signals that could be used to adjust OMR gain, such as retinal slip. Finally, the observation of diverse relationships between simple spikes and climbing fiber responses in individual Purkinje cells highlights the importance of distinguishing between these two types of activity in calcium imaging experiments.

scholarly journals Purkinje cell activity during classical conditioning with different conditional stimuli explains central tenet of Rescorla–Wagner model

2015 ◽  
Vol 112 (45) ◽  
pp. 14060-14065 ◽  
Author(s):  
Anders Rasmussen ◽  
Riccardo Zucca ◽  
Fredrik Johansson ◽  
Dan-Anders Jirenhed ◽  
Germund Hesslow
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Compound Stimulus ◽  
Eyeblink Conditioning ◽  
Unconditional Stimulus ◽  
Cell Activity ◽  
Neural Mechanisms ◽  
Wagner Model ◽  
Central Tenet ◽  
Reinforcement Value

A central tenet of Rescorla and Wagner’s model of associative learning is that the reinforcement value of a paired trial diminishes as the associative strength between the presented stimuli increases. Despite its fundamental importance to behavioral sciences, the neural mechanisms underlying the model have not been fully explored. Here, we present findings that, taken together, can explain why a stronger association leads to a reduced reinforcement value, within the context of eyeblink conditioning. Specifically, we show that learned pause responses in Purkinje cells, which trigger adaptively timed conditioned eyeblinks, suppress the unconditional stimulus (US) signal in a graded manner. Furthermore, by examining how Purkinje cells respond to two distinct conditional stimuli and to a compound stimulus, we provide evidence that could potentially help explain the somewhat counterintuitive overexpectation phenomenon, which was derived from the Rescorla–Wagner model.

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 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 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 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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