Over the past several decades, theories about cerebellar learning have evolved. A relatively simple view that highlighted the contribution of one major form of heterosynaptic plasticity to cerebellar ...motor learning has given way to a plethora of perspectives that suggest that many different forms of synaptic and non-synaptic plasticity, acting at various sites, can control multiple types of learning behaviour. However, there still seem to be contradictions between the various hypotheses with regard to the mechanisms underlying cerebellar learning. The challenge is therefore to reconcile these different views and unite them into a single overall concept. Here I review our current understanding of the changes in the activity of cerebellar Purkinje cells in different 'microzones' during various forms of learning. I describe an emerging model that indicates that the activity of each microzone is bound to either increase or decrease during the initial stages of learning, depending on the directional and temporal demands of its downstream circuitry and the behaviour involved.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Knowledge about the statistical regularities of the world is essential for cognitive and sensorimotor function. In the domain of timing, prior statistics are crucial for optimal prediction, ...adaptation and planning. Where and how the nervous system encodes temporal statistics is, however, not known. Based on physiological and anatomical evidence for cerebellar learning, we develop a computational model that demonstrates how the cerebellum could learn prior distributions of time intervals and support Bayesian temporal estimation. The model shows that salient features observed in human Bayesian time interval estimates can be readily captured by learning in the cerebellar cortex and circuit level computations in the cerebellar deep nuclei. We test human behavior in two cerebellar timing tasks and find prior-dependent biases in timing that are consistent with the predictions of the cerebellar model.
Key points
Directionality, inherent to movements, has behavioural and neuronal correlates.
Direction of vestibular stimulation determines motor learning efficiency.
Vestibulo‐ocular reflex ...gain–increase correlates with Purkinje cell simple spike potentiation.
The locus of neural correlates for vestibulo‐ocular reflex adaptation is paradigm specific.
Compensatory eye movements elicited by head rotation, also known as vestibulo‐ocular reflex (VOR), can be adapted with the use of visual feedback. The cerebellum is essential for this type of movement adaptation, although its neuronal correlates remain to be clarified. In the present study, we show that the direction of vestibular input determines the magnitude of eye movement adaptation induced by mismatched visual input in mice, with larger changes during contraversive head rotation. Moreover, the location of the neural correlate of this changed behaviour depends on the type of paradigm. Gain–increase paradigms induce increased simple spike (SS) activity in ipsilateral cerebellar Purkinje cells (PC), which is in line with eye movements triggered by optogenetic PC activation. By contrast, gain–decrease paradigms do not induce changes in SS activity, indicating that the murine vestibulo‐cerebellar cortical circuitry is optimally designed to enhance ipsiversive eye movements.
Key points
Directionality, inherent to movements, has behavioural and neuronal correlates.
Direction of vestibular stimulation determines motor learning efficiency.
Vestibulo‐ocular reflex gain–increase correlates with Purkinje cell simple spike potentiation.
The locus of neural correlates for vestibulo‐ocular reflex adaptation is paradigm specific.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Studies on synaptic plasticity in the context of learning have been dominated by the view that a single, particular type of plasticity forms the underlying mechanism for a particular type of ...learning. However, emerging evidence shows that many forms of synaptic and intrinsic plasticity at different sites are induced conjunctively during procedural memory formation in the cerebellum. Here, we review the main forms of long-term plasticity in the cerebellar cortex that underlie motor learning. We propose that the different forms of plasticity in the granular layer and the molecular layer operate synergistically in a temporally and spatially distributed manner, so as to ultimately create optimal output for behaviour.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The cerebellum fine-tunes motor activity via its Purkinje cell output. Purkinje cells produce two different types of spikes, complex spikes and simple spikes, which often show reciprocal activity: a ...periodical increase in complex spikes is associated with a decrease in simple spikes, and vice versa. This reciprocal firing is thought to be essential for coordinated motor behavior, yet how it is accomplished is debated. Here, we show in Ptf1a::cre;Robo3lox/lox mice that selectively rerouting the climbing fibers from a contralateral to an ipsilateral projection reversed the complex-spike modulation during sensory stimulation. Strikingly, modulation of simple spikes, which is supposed to be controlled by mossy fibers, reversed as well. Climbing fibers enforce this reciprocity in part by influencing activity of inhibitory interneurons, because the phase of their activity was also converted. Ptf1a::cre;Robo3lox/lox mice showed severe ataxia highlighting that climbing fiber input and its impact on reciprocity of Purkinje cell firing play an important role in motor coordination.
•Climbing fiber input dominates reciprocity of Purkinje cell firing•Complex-spike activity in Purkinje cells can override simple-spike firing patterns•Climbing fiber input contributes to modulation of molecular layer interneurons•Misrouting of climbing fiber pathway results in ataxia
The cerebellum fine-tunes motor activity via Purkinje cell output. Here, Badura et al. show that reciprocity of Purkinje cell complex and simple spike firing is shaped by climbing fiber activity. Disrupting reciprocity results in ataxia, highlighting the importance of climbing fiber input in motor coordination.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Local feedforward and recurrent connectivity are rife in the frontal areas of the cerebral cortex, which gives rise to rich heterogeneous dynamics observed in such areas. Recently, similar ...local connectivity motifs have been discovered among Purkinje and molecular layer interneurons of the cerebellar cortex, however, task-related activity in these neurons has often been associated with relatively simple facilitation and suppression dynamics. Here, we show that the rodent cerebellar cortex supports heterogeneity in task-related neuronal activity at a scale similar to the cerebral cortex. We provide a computational model that inculcates recent anatomical insights into local microcircuit motifs to show the putative basis for such heterogeneity. We also use cell-type specific chronic viral lesions to establish the involvement of cerebellar lobules in associative learning behaviors. Functional heterogeneity in neuronal profiles may not merely be the remit of the associative cerebral cortex, similar principles may be at play in subcortical areas, even those with seemingly crystalline and homogenous cytoarchitectures like the cerebellum.
Persistent and ramping neural activity in the frontal cortex anticipates specific movements
. Preparatory activity is distributed across several brain regions
, but it is unclear which brain areas ...are involved and how this activity is mediated by multi-regional interactions. The cerebellum is thought to be primarily involved in the short-timescale control of movement
; however, roles for this structure in cognitive processes have also been proposed
. In humans, cerebellar damage can cause defects in planning and working memory
. Here we show that persistent representation of information in the frontal cortex during motor planning is dependent on the cerebellum. Mice performed a sensory discrimination task in which they used short-term memory to plan a future directional movement. A transient perturbation in the medial deep cerebellar nucleus (fastigial nucleus) disrupted subsequent correct responses without hampering movement execution. Preparatory activity was observed in both the frontal cortex and the cerebellar nuclei, seconds before the onset of movement. The silencing of frontal cortex activity abolished preparatory activity in the cerebellar nuclei, and fastigial activity was necessary to maintain cortical preparatory activity. Fastigial output selectively targeted the behaviourally relevant part of the frontal cortex through the thalamus, thus closing a cortico-cerebellar loop. Our results support the view that persistent neural dynamics during motor planning is maintained by neural circuits that span multiple brain regions
, and that cerebellar computations extend beyond online motor control
.
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KISLJ, NUK, SBMB, UL, UM, UPUK
Neuronal firing, synaptic transmission, and its plasticity form the building blocks for processing and storage of information in the brain. It is unknown whether adult human synapses are more ...efficient in transferring information between neurons than rodent synapses. To test this, we recorded from connected pairs of pyramidal neurons in acute brain slices of adult human and mouse temporal cortex and probed the dynamical properties of use-dependent plasticity. We found that human synaptic connections were purely depressing and that they recovered three to four times more swiftly from depression than synapses in rodent neocortex. Thereby, during realistic spike trains, the temporal resolution of synaptic information exchange in human synapses substantially surpasses that in mice. Using information theory, we calculate that information transfer between human pyramidal neurons exceeds that of mouse pyramidal neurons by four to nine times, well into the beta and gamma frequency range. In addition, we found that human principal cells tracked fine temporal features, conveyed in received synaptic inputs, at a wider bandwidth than for rodents. Action potential firing probability was reliably phase-locked to input transients up to 1,000 cycles/s because of a steep onset of action potentials in human pyramidal neurons during spike trains, unlike in rodent neurons. Our data show that, in contrast to the widely held views of limited information transfer in rodent depressing synapses, fast recovering synapses of human neurons can actually transfer substantial amounts of information during spike trains. In addition, human pyramidal neurons are equipped to encode high synaptic information content. Thus, adult human cortical microcircuits relay information at a wider bandwidth than rodent microcircuits.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diversity and dynamism in the cerebellum De Zeeuw, Chris I; Lisberger, Stephen G; Raymond, Jennifer L
Nature neuroscience,
02/2021, Volume:
24, Issue:
2
Journal Article
Peer reviewed
The past several years have brought revelations and paradigm shifts in research on the cerebellum. Historically viewed as a simple sensorimotor controller with homogeneous architecture, the ...cerebellum is increasingly implicated in cognitive functions. It possesses an impressive diversity of molecular, cellular and circuit mechanisms, embedded in a dynamic, recurrent circuit architecture. Recent insights about the diversity and dynamism of the cerebellum provide a roadmap for the next decade of cerebellar research, challenging some old concepts, reinvigorating others and defining major new research directions.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
During development, cortical plasticity is associated with the rearrangement of excitatory connections. While these connections become more stable with age, plasticity can still be induced in the ...adult cortex. Here we provide evidence that structural plasticity of inhibitory synapses onto pyramidal neurons is a major component of plasticity in the adult neocortex. In vivo two-photon imaging was used to monitor the formation and elimination of fluorescently labeled inhibitory structures on pyramidal neurons. We find that ocular dominance plasticity in the adult visual cortex is associated with rapid inhibitory synapse loss, especially of those present on dendritic spines. This occurs not only with monocular deprivation but also with subsequent restoration of binocular vision. We propose that in the adult visual cortex the experience-induced loss of inhibition may effectively strengthen specific visual inputs with limited need for rearranging the excitatory circuitry.
► Plasticity in adult visual cortex is associated with rapid inhibitory synapse loss ► This loss of inhibition is matched by increased visual responsiveness ► Inhibitory synapse loss occurs predominantly on stable dendritic spines ► This may allow adult plasticity despite reduced plasticity of excitatory synapses
van Versendaal et al. show that plasticity in the adult visual cortex is associated with the rapid loss of inhibitory synapses. This may represent a mechanism allowing adult plasticity to occur without the need for extensive reorganization of excitatory synapses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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