Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning

Giovannucci, Andrea; Badura, Aleksandra; Deverett, Ben; Najafi, Farzaneh; Pereira, Talmo; Gao, Zhenyu; Ozden, Ilker; Kloth, Alexander D.; Pnevmatikakis, Eftychios A.; Paninski, Liam; Zeeuw, Chris I. De; Medina, Javier F.; Wang, Samuel S.‐H.

doi:10.1038/nn.4531

Cited by 202 publications

(258 citation statements)

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“…Experiments that drive cerebellar activity via bottom‐up climbing fiber error signals may be unsuited to measurement by fMRI, whereas experiments that drive cerebellar activity via mossy fiber inputs may lead to detectable BOLD responses (Diedrichsen, Verstynen, Schlerf, & Wiestler, ). This is consistent with the view that the mossy fiber input system is more strongly associated with processes of motor learning in adapting to sensorimotor prediction errors (Giovannucci et al, ; Ito, ; Thach, ).…”

Section: Discussionsupporting

confidence: 90%

The role of the cerebellum in adaptation: ALE meta‐analyses on sensory feedback error

Johnson

Belyk

Schwartze

et al. 2019

Human Brain Mapping

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It is widely accepted that unexpected sensory consequences of self‐action engage the cerebellum. However, we currently lack consensus on where in the cerebellum, we find fine‐grained differentiation to unexpected sensory feedback. This may result from methodological diversity in task‐based human neuroimaging studies that experimentally alter the quality of self‐generated sensory feedback. We gathered existing studies that manipulated sensory feedback using a variety of methodological approaches and performed activation likelihood estimation (ALE) meta‐analyses. Only half of these studies reported cerebellar activation with considerable variation in spatial location. Consequently, ALE analyses did not reveal significantly increased likelihood of activation in the cerebellum despite the broad scientific consensus of the cerebellum's involvement. In light of the high degree of methodological variability in published studies, we tested for statistical dependence between methodological factors that varied across the published studies. Experiments that elicited an adaptive response to continuously altered sensory feedback more frequently reported activation in the cerebellum than those experiments that did not induce adaptation. These findings may explain the surprisingly low rate of significant cerebellar activation across brain imaging studies investigating unexpected sensory feedback. Furthermore, limitations of functional magnetic resonance imaging to probe the cerebellum could play a role as climbing fiber activity associated with feedback error processing may not be captured by it. We provide methodological recommendations that may guide future studies.

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Section: Discussionsupporting

confidence: 90%

The role of the cerebellum in adaptation: ALE meta‐analyses on sensory feedback error

Johnson

Belyk

Schwartze

et al. 2019

Human Brain Mapping

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“…Enhancement of these signals may be driven, in part, from conjunctive activity of parallel fibers (Giovannucci et al, 2017). In this scenario, enhanced climbing fiber-evoked Ca 2+ signaling in PCs during learning may arise from alterations in network activity within the cerebellar cortex.…”

Section: Discussionmentioning

confidence: 99%

Inhibition gates supralinear Ca2+ signaling in Purkinje cell dendrites during practiced movements

Gaffield

Rowan

Amat

et al. 2018

eLife

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Motor learning involves neural circuit modifications in the cerebellar cortex, likely through re-weighting of parallel fiber inputs onto Purkinje cells (PCs). Climbing fibers instruct these synaptic modifications when they excite PCs in conjunction with parallel fiber activity, a pairing that enhances climbing fiber-evoked Ca2+ signaling in PC dendrites. In vivo, climbing fibers spike continuously, including during movements when parallel fibers are simultaneously conveying sensorimotor information to PCs. Whether parallel fiber activity enhances climbing fiber Ca2+ signaling during motor behaviors is unknown. In mice, we found that inhibitory molecular layer interneurons (MLIs), activated by parallel fibers during practiced movements, suppressed parallel fiber enhancement of climbing fiber Ca2+ signaling in PCs. Similar results were obtained in acute slices for brief parallel fiber stimuli. Interestingly, more prolonged parallel fiber excitation revealed latent supralinear Ca2+ signaling. Therefore, the balance of parallel fiber and MLI input onto PCs regulates concomitant climbing fiber Ca2+ signaling.

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“…In the vestibulocerebellum, granule cells exhibit a range of responses to vestibular stimuli, including high-frequency bursts of spikes, sustained firing with smooth firing rate modulation in response to the vestibular stimulus, or, in some granule cells, a combination of both response types [72]. Likewise, calcium imaging studies suggest that many granule cells have high levels of sustained activity in awake behaving animals [73–75], although this approach does not provide spike-level resolution of granule cell activity.…”

Section: Biologically Plausible Variations That May Influence the Indmentioning

confidence: 99%

“…A prominent and compelling theory proposes sparse coding of information by granule cells [76–79]. However, recent imaging studies challenge the hypothesis that activation of the granule cell population is sparse in behaving animals [73,74,80,81]. In vitro , the number of co-activated parallel fibers, which can be controlled by the strength of parallel fiber stimulation, can influence whether LTD is induced or not [67,68], suggesting that cooperativity at parallel fiber synapses is an important consideration.…”

Section: Biologically Plausible Variations That May Influence the Indmentioning

confidence: 99%

Depressed by Learning—Heterogeneity of the Plasticity Rules at Parallel Fiber Synapses onto Purkinje Cells

Suvrathan

Raymond

2018

Cerebellum

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Climbing fiber-driven long-term depression (LTD) of parallel fiber synapses onto cerebellar Purkinje cells has long been investigated as a putative mechanism of motor learning. We recently discovered that the rules governing the induction of LTD at these synapses vary across different regions of the cerebellum. Here, we discuss the design of LTD induction protocols in light of this heterogeneity in plasticity rules. The analytical advantages of the cerebellum provide an opportunity to develop a deeper understanding of how the specific plasticity rules at synapses support the implementation of learning.

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Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning

Cited by 202 publications

References 50 publications

The role of the cerebellum in adaptation: ALE meta‐analyses on sensory feedback error

The role of the cerebellum in adaptation: ALE meta‐analyses on sensory feedback error

Inhibition gates supralinear Ca2+ signaling in Purkinje cell dendrites during practiced movements

Depressed by Learning—Heterogeneity of the Plasticity Rules at Parallel Fiber Synapses onto Purkinje Cells

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