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| Open AccessOrganization of reward and movement signals in the basal ganglia and cerebellum
How the brain transforms reward information into actions remains poorly understood. Here, the authors found that reward expectation and sensorimotor signals are more pronounced in the output of the basal ganglia than its input or the cerebellar cortex, implying that the transformation of reward signals into motor signals is not hierarchically organized.
- Noga Larry
- , Gil Zur
- & Mati Joshua
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Article
| Open AccessHeterogeneous encoding of temporal stimuli in the cerebellar cortex
The frontal cortex shows intricate feedback and feedforward connectivity, but other brain areas such as the cerebellum are thought to exhibit simpler activity profiles. Here, the authors show that rodent cerebellar cortex supports heterogeneity in task-related neuronal activity at a scale similar to that in the cerebral cortex.
- Chris. I. De Zeeuw
- , Julius Koppen
- & Devika Narain
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| Open AccessPurkinje cell microzones mediate distinct kinematics of a single movement
Purkinje cells form a diverse population, but how diversity contributes to cerebellar behavior is not fully understood. Here, the authors reveal how nuances in molecular signatures correlate with electrophysiological, anatomical, and ultimately functional differences among Purkinje cell subpopulations.
- François G. C. Blot
- , Joshua J. White
- & Martijn Schonewille
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| Open AccessReinforcement learning establishes a minimal metacognitive process to monitor and control motor learning performance
Metacognition is fundamental for regulating learning speeds and memory retention. Here, the authors demonstrate that reinforcement learning mediates this process in implicit motor learning, maximizing rewards and minimizing punishments.
- Taisei Sugiyama
- , Nicolas Schweighofer
- & Jun Izawa
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Article
| Open AccessGlutamatergic cerebellar neurons differentially contribute to the acquisition of motor and social behaviors
Cerebellar injury in early life can impair the development of motor and social behaviors. Here, the authors show that cerebellar cell types are differentially important for the acquisition of these behaviors in pups and adult mice.
- Meike E. van der Heijden
- , Alejandro G. Rey Hipolito
- & Roy V. Sillitoe
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| Open AccessMultidimensional cerebellar computations for flexible kinematic control of movements
Moving precisely in natural environments requires adapting to multiple demands arising dynamically. Here, the authors show that the cerebellum’s capacity for multidimensional computations allows it to flexibly control multiple movement parameters guaranteeing movement precision.
- Akshay Markanday
- , Sungho Hong
- & Peter Thier
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| Open AccessPurkinje cell dopaminergic inputs to astrocytes regulate cerebellar-dependent behavior
The role of dopamine in the cerebellum remains relatively unexplored. Here, the authors report a dopamine system in the cerebellum in mice, where Purkinje cells supply dopamine and Bergmann glia express D1 receptors. Activation of D1 receptors is found to modulate Purkinje cell activity and to affect locomotor and social behaviors.
- Chang Li
- , Natalie B. Saliba
- & Wei Li
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| Open AccessCerebro-cerebellar networks facilitate learning through feedback decoupling
Behavioral feedback is critical for learning, but it is often not available. Here, the authors introduce a deep learning model in which the cerebellum provides the cerebrum with feedback predictions, thereby facilitating learning, reducing dysmetria, and making several experimental predictions.
- Ellen Boven
- , Joseph Pemberton
- & Rui Ponte Costa
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| Open AccessSynaptic basis of a sub-second representation of time in a neural circuit model
Neural circuit dynamics are thought to drive temporally precise actions. Here, the authors used a theoretical approach to show that synapses endowed with diverse short-term plasticity can act as tunable timers sufficient to generate rich neural dynamics.
- A. Barri
- , M. T. Wiechert
- & D. A. DiGregorio
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| Open AccessNeural signals regulating motor synchronization in the primate deep cerebellar nuclei
It remains unclear how the brain represents information regarding synchronized movements. Here, the authors investigated the response properties of cerebellar cells in macaques performing a synchronized saccade task and found three groups of cerebellar neurons with distinct peri-saccade response profiles.
- Ken-ichi Okada
- , Ryuji Takeya
- & Masaki Tanaka
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| Open AccessCerebellar connectivity maps embody individual adaptive behavior in mice
The variability in synaptic connectivity observed at the cerebellar granule cell - Purkinje cell connection in mice accounts for motor behavior traits at the individual level, suggesting that cerebellar networks encode internal models underlying individual-specific motor adaptation.
- Ludovic Spaeth
- , Jyotika Bahuguna
- & Philippe Isope
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| Open AccessA cerebellar internal model calibrates a feedback controller involved in sensorimotor control
Animals can adjust their behavior in response to changes in the environment when these changes can be predicted. Here the authors show the role of the cerebellum in zebrafish that change their swimming as they adjust to long-lasting changes in visual feedback
- Daniil A. Markov
- , Luigi Petrucco
- & Ruben Portugues
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| Open AccessMid-lateral cerebellar complex spikes encode multiple independent reward-related signals during reinforcement learning
The role of complex spikes in reinforcement learning is still unclear. Here, the authors show that complex spikes carry multiple context based, cell type specific and learning dependent signals that are independent of changes in any motor kinematics and unlikely to instruct the concurrent simple spike activity during reinforcement learning.
- Naveen Sendhilnathan
- , Anna Ipata
- & Michael E. Goldberg
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| Open AccessAutonomous Purkinje cell activation instructs bidirectional motor learning through evoked dendritic calcium signaling
Plastic reweighting of parallel fiber synaptic strength is a mechanism for the acquisition of cerebellum-dependent motor learning. Here, the authors found that optogenetic activation of PCs generates dendritic Ca2+ signals that induce plasticity in vitro and instruct learned changes to coincident eye movements in vivo.
- Audrey Bonnan
- , Matthew M. J. Rowan
- & Jason M. Christie
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| Open AccessNeuromodulation of the cerebellum rescues movement in a mouse model of ataxia
Deep brain stimulation (DBS) has potential for several movement disorders. Here the authors show that DBS improves motor function in a mouse model of ataxia.
- Lauren N. Miterko
- , Tao Lin
- & Roy V. Sillitoe
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| Open AccessEthanol abolishes vigilance-dependent astroglia network activation in mice by inhibiting norepinephrine release
The effects of norepinephrine on sensory processing in cortical networks are altered by recreational drugs like ethanol. The authors show that ethanol suppresses the activation of astrocytes by inhibiting norepinephrine release which may contribute to the cognitive effects of alcohol intoxication.
- Liang Ye
- , Murat Orynbayev
- & Martin Paukert
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| Open AccessA FN-MdV pathway and its role in cerebellar multimodular control of sensorimotor behavior
Delay eyeblink conditioning depends on the simplex lobule-interposed nucleus pathway in the cerebellum. Here, the authors show that the vermis-fastigial nucleus-medullary reticular nucleus pathway modulates the conditioned and unconditioned eyelid closure during delay eyeblink conditioning.
- Xiaolu Wang
- , Si-yang Yu
- & Zhenyu Gao
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Article
| Open AccessComparative analysis of squamate brains unveils multi-level variation in cerebellar architecture associated with locomotor specialization
The cerebellum is critical in sensory-motor control and is structurally diverse across vertebrates. Here, the authors investigate the evolutionary relationship between locomotory mode and cerebellum architecture across squamates by integrating study of gene expression, cell distribution, and 3D morphology.
- Simone Macrì
- , Yoland Savriama
- & Nicolas Di-Poï
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| Open AccessImpaired cerebellar Purkinje cell potentiation generates unstable spatial map orientation and inaccurate navigation
It is known that Purkinje cell PKC-dependent depression is involved in the stabilization of self-motion based hippocampal representation. Here the authors describe decreased stability of hippocampal place cells based on allocentric cues in mice lacking Purkinje cell PP2B-dependent potentiation.
- Julie Marie Lefort
- , Jean Vincent
- & Christelle Rochefort
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| Open AccessNeonatal brain injury causes cerebellar learning deficits and Purkinje cell dysfunction
Premature infants are vulnerable to hypoxia and thus white matter injury, especially in the cerebellum, which develops during late gestation. Here, the authors test the effects of perinatal hypoxia on motor performance and rescue behavioral deficits using the GABA reuptake inhibitor Tiagabine.
- Aaron Sathyanesan
- , Srikanya Kundu
- & Vittorio Gallo
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| Open AccessElongator mutation in mice induces neurodegeneration and ataxia-like behavior
Elp6 is a component of the Elongator complex that regulates tRNAs and translation. Here the authors identify a mutation in the Elp6 gene that contributes to the cerebellar ataxia-like phenotype in a mutant mouse.
- Marija Kojic
- , Monika Gaik
- & Brandon J. Wainwright
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| Open AccessModulation of sensory prediction error in Purkinje cells during visual feedback manipulations
Cerebellum is thought to encode predictions about upcoming movements and provide a sensory prediction error based on the actual movement. Here the authors manipulate visual feedback during a movement-tracking task to show that both signals are carried in the lead and lag modulations of simple spikes of Purkinje cells.
- Martha L. Streng
- , Laurentiu S. Popa
- & Timothy J. Ebner
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| Open AccessSerial processing of kinematic signals by cerebellar circuitry during voluntary whisking
Cerebellar Purkinje cells (PCs) linearly encode whisker position but the precise circuit mechanisms that generate these signals are not well understood. Here the authors use patch clamp recordings to show that selective tuning of granule cell inputs and bidirectional tuning of interneuron inputs are required to generate the kinematic representations in PCs.
- Susu Chen
- , George J. Augustine
- & Paul Chadderton
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| Open AccessGenetic silencing of olivocerebellar synapses causes dystonia-like behaviour in mice
Dystonia is thought to be driven by impairments in cerebellar signalling. The authors use a mouse genetic approach to silence excitatory transmission in the inferior olive to cerebellum pathway, resulting in dystonia-like signs in the animals which can be alleviated using DBS stimulation of the pathway.
- Joshua J. White
- & Roy V. Sillitoe
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| Open AccessDendritic excitation–inhibition balance shapes cerebellar output during motor behaviour
Here, the authors combinein vivopatch-clamp recordings and optogenetics to show that balanced dendritic excitation and inhibition provides a sensitive ‘push-pull’ mechanism that generates the bidirectional modulation of Purkinje cell SSp output necessary for normal locomotor behaviour.
- Marta Jelitai
- , Paolo Puggioni
- & Ian Duguid
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| Open AccessDysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice
Mutations in SHANK2 are associated with autism spectrum disorders (ASD). Here, Peter et al. show that selective loss of Shank2in Purkinje cells of the mouse cerebellum leads to deficits in plasticity, motor behaviour, and a social behaviour phenotype similar to that seen in ASD.
- Saša Peter
- , Michiel M. ten Brinke
- & Chris I. De Zeeuw
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| Open AccessGenetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum
This genome-wide association study identifies five significant SNPs in two loci which are associated with the epigenetic age of post-mortem cerebellar tissue according to a DNA methylation based biomarker of human aging.
- Ake T. Lu
- , Eilis Hannon
- & Steve Horvath
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Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism
Impairments of cerebellar-dependent motor control and learning are implicated in some forms of autism spectrum disorder (ASD). In this study, the authors provide a characterization of the motor deficits and cerebellar function abnormalities in a transgenic mouse model of ASD.
- Claire Piochon
- , Alexander D. Kloth
- & Christian Hansel
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| Open AccessSnf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation
The chromatin remodelling proteins Snf2h and Snf2l regulate nucleosome spacing. Here, the authors show that Snf2hablation impairs chromatin organization of neuronal lineages during mouse embryonic and post-natal cerebellar development.
- Matías Alvarez-Saavedra
- , Yves De Repentigny
- & David J. Picketts
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Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum
GABAergic neuron progenitors in the cerebellum give rise to Purkinje cells and GABAergic interneurons. Here the authors show that the transcription factors Olig2 and Gsx1 regulate an identity transition from Purkinje cell progenitors to interneuron progenitors during mouse development.
- Yusuke Seto
- , Tomoya Nakatani
- & Mikio Hoshino
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| Open AccessSpike timing-dependent selective strengthening of single climbing fibre inputs to Purkinje cells during cerebellar development
Cerebellar development involves activity-dependent strengthening of synaptic contacts between climbing fibres and Purkinje cells. Kawamura et al.show that temporally clustered multiple climbing fibre inputs contribute to characteristic burst spiking in immature Purkinje cells before specific contacts are strengthened.
- Yoshinobu Kawamura
- , Hisako Nakayama
- & Masanobu Kano
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Unravelling cerebellar pathways with high temporal precision targeting motor and extensive sensory and parietal networks
The cerebellum has important roles in motor control and sensory perception. Sultan and colleagues use electrical stimulation and functional magnetic resonance imaging to reveal that the cerebellum provides inputs to specialized cortical regions of the brain that modulate cerebro-cortical processing.
- Fahad Sultan
- , Mark Augath
- & Peter Thier