scholarly journals A recurrent circuit links antagonistic cerebellar modules during associative motor learning

2021 ◽  
Author(s):  
Shogo Ohmae ◽  
Keiko Ohmae ◽  
Shane A Heiney ◽  
Divya Subramanian ◽  
Javier F Medina
Keyword(s):  
Purkinje Cells ◽  
Functional Organization ◽  
Eyeblink Conditioning ◽  
Recurrent Network ◽  
Basic Operation ◽  
Conventional View ◽  
Neural Architecture ◽  
Recurrent Network Dynamics ◽  
Cerebellar Modules ◽  
Specific Error

The neural architecture of the cerebellum is thought to be specialized for performing supervised learning: specific error-related climbing fiber inputs are used to teach sensorimotor associations to small ensembles of Purkinje cells located in functionally distinct modules that operate independently of each other in a purely feedforward manner. Here, we test whether the basic operation of the cerebellum complies with this basic architecture in mice that learned a simple sensorimotor association during eyeblink conditioning. By recording Purkinje cells in different modules and testing whether their responses rely on recurrent circuits, our results reveal three operational principles about the functional organization of the cerebellum that stand in stark contrast to the conventional view: (1) Antagonistic organization, (2) Recurrent network dynamics, and (3) Intermodular communication. We propose that the neural architecture of the cerebellum implements these three operational principles to achieve optimal performance and solve a number of problems in motor control.

scholarly journals A FN-MdV pathway and its role in cerebellar multimodular control of sensorimotor behavior

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaolu Wang ◽  
Si-yang Yu ◽  
Zhong Ren ◽  
Chris I. De Zeeuw ◽  
Zhenyu Gao
Keyword(s):  
Purkinje Cells ◽  
Motor Neurons ◽  
Eyeblink Conditioning ◽  
Fastigial Nucleus ◽  
Reticular Nucleus ◽  
Eyelid Closure ◽  
Interposed Nucleus ◽  
Conditioned Responses ◽  
Cerebellar Modules ◽  
Synergistic Modulation

AbstractThe cerebellum is crucial for various associative sensorimotor behaviors. Delay eyeblink conditioning (DEC) depends on the simplex lobule-interposed nucleus (IN) pathway, yet it is unclear how other cerebellar modules cooperate during this task. Here, we demonstrate the contribution of the vermis-fastigial nucleus (FN) pathway in controlling DEC. We found that task-related modulations in vermal Purkinje cells and FN neurons predict conditioned responses (CRs). Coactivation of the FN and the IN allows for the generation of proper motor commands for CRs, but only FN output fine-tunes unconditioned responses. The vermis-FN pathway launches its signal via the contralateral ventral medullary reticular nucleus, which converges with the command from the simplex-IN pathway onto facial motor neurons. We propose that the IN pathway specifically drives CRs, whereas the FN pathway modulates the amplitudes of eyelid closure during DEC. Thus, associative sensorimotor task optimization requires synergistic modulation of different olivocerebellar modules each provide unique contributions.

scholarly journals A Novel FN-MdV Pathway and Its Role in Cerebellar Multimodular Control of Sensorimotor Behavior

2020 ◽  
Author(s):  
Xiaolu Wang ◽  
Si-yang Yu ◽  
Zhong Ren ◽  
Chris De Zeeuw ◽  
Zhenyu Gao
Keyword(s):  
Purkinje Cells ◽  
Motor Neurons ◽  
Eyeblink Conditioning ◽  
Fastigial Nucleus ◽  
Reticular Nucleus ◽  
Eyelid Closure ◽  
Interposed Nucleus ◽  
Conditioned Responses ◽  
Cerebellar Modules ◽  
Synergistic Modulation

Abstract The cerebellum is crucial for various associative sensorimotor behaviors. Delay eyeblink conditioning (DEC) depends on the simplex lobule-interposed nucleus (IN) pathway, yet it is unclear how other cerebellar modules cooperate during this task. Here, we demonstrate the contribution of the vermis-fastigial nucleus (FN) pathway in controlling DEC. We found that task-related modulations in vermal Purkinje cells and FN neurons predict conditioned responses (CRs). Coactivation of the FN and the IN allows for the generation of proper motor commands for CRs, but only FN output fine-tunes unconditioned responses. The vermis-FN pathway launches its signal via the contralateral ventral medullary reticular nucleus, which converges with the command from the simplex-IN pathway onto facial motor neurons. We propose that the IN pathway specifically drives CRs whereas the FN pathway modulates the amplitudes of eyelid closure during DEC. Thus, associative sensorimotor task optimization requires synergistic modulation of different olivocerebellar modules that provide unique contributions.

scholarly journals Differential spatiotemporal development of Purkinje cell populations and cerebellum-dependent sensorimotor behaviors

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Gerrit Cornelis Beekhof ◽  
Catarina Osório ◽  
Joshua J White ◽  
Scott van Zoomeren ◽  
Hannah van der Stok ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Eyeblink Conditioning ◽  
Rapid Development ◽  
Modular Organization ◽  
Cell Populations ◽  
Activity Levels ◽  
Firing Activity ◽  
The Core ◽  
Cerebellar Modules

Distinct populations of Purkinje cells (PCs) with unique molecular and connectivity features are at the core of the modular organization of the cerebellum. Previously, we showed that firing activity of Purkinje cells differs between ZebrinII-positive (Z+) and -negative (Z−) cerebellar modules (Zhou et al., 2014; Wu et al., 2019). Here, we investigate the timing and extent of PC differentiation during development in mice. We found that several features of PCs, including activity levels, dendritic arborisation, axonal shape and climbing fiber input, develop differentially between nodular and anterior PC populations. Although all PCs show a particularly rapid development in the second postnatal week, anterior PCs typically have a prolonged physiological and dendritic maturation. In line herewith, younger mice exhibit attenuated anterior-dependent eyeblink conditioning, but faster nodular-dependent compensatory eye movement adaptation. Our results indicate that specific cerebellar regions have unique developmental timelines which match with their related, specific forms of cerebellum-dependent behaviors.

scholarly journals Stereotyped spatial patterns of functional synaptic connectivity in the cerebellar cortex

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Antoine M Valera ◽  
Francesca Binda ◽  
Sophie A Pawlowski ◽  
Jean-Luc Dupont ◽  
Jean-François Casella ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Granule Cell ◽  
Motor Coordination ◽  
Molecular Layer ◽  
Granule Cell Layer ◽  
Synaptic Organization ◽  
Cerebellar Modules ◽  
Activity Dependent

Motor coordination is supported by an array of highly organized heterogeneous modules in the cerebellum. How incoming sensorimotor information is channeled and communicated between these anatomical modules is still poorly understood. In this study, we used transgenic mice expressing GFP in specific subsets of Purkinje cells that allowed us to target a given set of cerebellar modules. Combining in vitro recordings and photostimulation, we identified stereotyped patterns of functional synaptic organization between the granule cell layer and its main targets, the Purkinje cells, Golgi cells and molecular layer interneurons. Each type of connection displayed position-specific patterns of granule cell synaptic inputs that do not strictly match with anatomical boundaries but connect distant cortical modules. Although these patterns can be adjusted by activity-dependent processes, they were found to be consistent and predictable between animals. Our results highlight the operational rules underlying communication between modules in the cerebellar cortex.

scholarly journals Generic Homo sapiens and Unique Mus musculus: Establishing the Typicality of the Modeled and the Model Species

2019 ◽  
Vol 93 (2-3) ◽  
pp. 122-136 ◽  
Author(s):  
Barbara L. Finlay
Keyword(s):  
Neural Development ◽  
Functional Organization ◽  
Homo Sapiens ◽  
Laboratory Mouse ◽  
Mouse Strains ◽  
Human Species ◽  
Model Species ◽  
Brain Mass ◽  
Multiple Strategies ◽  
Neural Architecture

The question of how complex human abilities evolved, such as language or face recognition, has been pursued by means of multiple strategies. Highly specialized non-human species have been examined analytically for formal similarities, close phylogenetic relatives have been examined for continuity, and simpler species have been analyzed for the broadest view of functional organization. All these strategies require empirical evidence of what is variable and predictable in both the modeled and the model species. Turning to humans, allometric analyses of the evolution of brain mass and brain components often return the interesting, but disappointing answer that volumetric organization of the human brain is highly predictable seen in its phylogenetic context. Reconciling this insight with unique human behavior, or any species-typical behavior, represents a serious challenge. Allometric analyses of the order and duration of mammalian neural development show that, while basic neural development in humans is allometrically predictable, conforming to adult neural architecture, some life history features deviate, notably that weaning is unusually early. Finally, unusual deviations in the retina and central auditory system in the laboratory mouse, which is widely assumed to be “generic,” as well as severe deviations from expected brain allometry in some mouse strains, underline the need for a deeper understanding of phylogenetic variability even in those systems believed to be best understood.

Layer-specific excitatory circuits differentially control recurrent network dynamics in the neocortex

2013 ◽  
Vol 16 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Riccardo Beltramo ◽  
Giulia D'Urso ◽  
Marco Dal Maschio ◽  
Pasqualina Farisello ◽  
Serena Bovetti ◽  
...  
Keyword(s):  
Network Dynamics ◽  
Recurrent Network ◽  
Recurrent Network Dynamics

scholarly journals TRPC3 is essential for functional heterogeneity of cerebellar Purkinje cells

2018 ◽  
Author(s):  
Bin Wu ◽  
Francois G.C. Blot ◽  
Aaron B. Wong ◽  
Catarina Osório ◽  
Youri Adolfs ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Transient Receptor Potential ◽  
Eyeblink Conditioning ◽  
Receptor Potential ◽  
Cellular Heterogeneity ◽  
Loss Of Function ◽  
Functional Heterogeneity ◽  
Homogeneous Population ◽  
Cerebellar Purkinje Cells

AbstractDespite the canonical homogenous character of its organization, the cerebellum plays differential computational roles in distinct types of sensorimotor behaviors. However, the molecular and cell physiological underpinnings are unclear. Here we determined the contribution of transient receptor potential cation channel type C3 (TRPC3) to signal processing in different cerebellar modules. Using gain-of-function and loss-of-function mouse models, we found that TRPC3 controls the simple spike activity of zebrin-negative (Z–), but not of zebrin-positive (Z+), Purkinje cells. Moreover, in vivo TRPC3 also regulated complex spike firing and its interaction with simple spikes exclusively in Z– Purkinje cells. Finally, we found that eyeblink conditioning, related to Z– modules, but not compensatory eye movement adaptation, linked to Z+ modules, was affected in TRPC3 loss-of-function mice. Together, our results indicate that TRPC3 is essential for the cellular heterogeneity that introduces distinct physiological properties in an otherwise homogeneous population of Purkinje cells, conjuring functional heterogeneity in cerebellar sensorimotor integration.

Effect of Conditioned Stimulus Parameters on Timing of Conditioned Purkinje Cell Responses

2010 ◽  
Vol 103 (3) ◽  
pp. 1329-1336 ◽  
Author(s):  
Pär Svensson ◽  
Dan-Anders Jirenhed ◽  
Fredrik Bengtsson ◽  
Germund Hesslow
Keyword(s):  
Conditioned Stimulus ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Mossy Fiber ◽  
Eyeblink Conditioning ◽  
Mossy Fibers ◽  
Inhibitory Response ◽  
Cell Responses ◽  
Cerebellar Purkinje Cells ◽  
Adaptive Timing

Pavlovian eyeblink conditioning is a useful experimental model for studying adaptive timing, an important aspect of skilled movements. The conditioned response (CR) is precisely timed to occur just before the onset of the expected unconditioned stimulus (US). The timing can be changed immediately, however, by varying parameters of the conditioned stimulus (CS). It has previously been shown that increasing the intensity of a peripheral CS or the frequency of a CS consisting of a train of stimuli to the mossy fibers shortens the latency of the CR. The adaptive timing of behavioral CRs probably reflects the timing of an underlying learned inhibitory response in cerebellar Purkinje cells. It is not known how the latency of this Purkinje cell CR is controlled. We have recorded form Purkinje cells in conditioned decerebrate ferrets while increasing the intensity of a peripheral CS or the frequency of a mossy fiber CS. We observe changes in the timing of the Purkinje cell CR that match the behavioral effects. The results are consistent with the effect of CS parameters on behavioral CR latency being caused by corresponding changes in Purkinje cell CRs. They suggest that synaptic temporal summation may be one of several mechanisms underlying adaptive timing of movements.

scholarly journals Learned response sequences in cerebellar Purkinje cells

2017 ◽  
Vol 114 (23) ◽  
pp. 6127-6132 ◽  
Author(s):  
Dan-Anders Jirenhed ◽  
Anders Rasmussen ◽  
Fredrik Johansson ◽  
Germund Hesslow
Keyword(s):  
Purkinje Cells ◽  
Interstimulus Interval ◽  
Response Pattern ◽  
Mossy Fiber ◽  
Eyeblink Conditioning ◽  
Complex Motor ◽  
Cerebellar Purkinje Cells ◽  
Single Response ◽  
The Right ◽  
Stimulation Of

Associative learning in the cerebellum has previously focused on single movements. In eyeblink conditioning, for instance, a subject learns to blink at the right time in response to a conditional stimulus (CS), such as a tone that is repeatedly followed by an unconditional corneal stimulus (US). During conditioning, the CS and US are transmitted by mossy/parallel fibers and climbing fibers to cerebellar Purkinje cells that acquire a precisely timed pause response that drives the overt blink response. The timing of this conditional Purkinje cell response is determined by the CS–US interval and is independent of temporal patterns in the input signal. In addition to single movements, the cerebellum is also believed to be important for learning complex motor programs that require multiple precisely timed muscle contractions, such as, for example, playing the piano. In the present work, we studied Purkinje cells in decerebrate ferrets that were conditioned using electrical stimulation of mossy fiber and climbing fiber afferents as CS and US, while alternating between short and long interstimulus intervals. We found that Purkinje cells can learn double pause responses, separated by an intermediate excitation, where each pause corresponds to one interstimulus interval. The results show that individual cells can not only learn to time a single response but that they also learn an accurately timed sequential response pattern.

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