Cerebellar Purkinje cell activity drives motor learning

Nguyen-Vu, TD Barbara; Kimpo, Rhea R.; Rinaldi, Jacob; Kohli, Arjun H.; Zeng, Hongkui; Deisseroth, Karl; Raymond, Jennifer L.

doi:10.1038/nn.3576

Cited by 129 publications

(143 citation statements)

References 32 publications

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“…Together these results indicate a prominent role of the cerebellum in the after effects of motor training. The central role of the cerebellum and cortico-cerebellar loops in motor learning are consistent with existent literature (Raymond et al, 1996;Inoue et al, 2000;Della-Maggiore et al, 2009;Nguyen-Vu et al, 2013).…”

Section: Discussionsupporting

confidence: 90%

Upregulation of cortico-cerebellar functional connectivity after motor learning

et al. 2016

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Interactions between the cerebellum and primary motor cortex are crucial for the acquisition of new motor skills. Recent neuroimaging studies indicate that learning motor skills is associated with subsequent modulation of resting-state functional connectivity in the cerebellar and cerebral cortices. The neuronal processes underlying the motor-learning induced plasticity are not well understood. Here, we investigate changes in functional connectivity in source-reconstructed electroencephalography (EEG) following the performance of a single session of a dynamic force task in twenty young adults. Source activity was reconstructed in 112 regions of interest (ROIs) and the functional connectivity between all ROIs was estimated using imaginary part of the coherence. Significant changes in resting-state connectivity were assessed using partial least squares (PLS). We found that subjects adapted their motor performance during the training session and showed improved accuracy but with slower movement times. A number of connections were significantly upregulated after motor training, principally involving connections within the cerebellum and between the cerebellum and motor cortex. Increased connectivity was confined to specific frequency ranges in the mu and beta bands. Post-hoc analysis of the phase spectra of these cerebellar and corticocerebellar connections revealed an increased phase-lag between motor cortical and cerebellar activity following motor practice. These findings show a reorganization of intrinsic corticocerebellar connectivity related to motor adaption and demonstrate the potential of EEG connectivity analysis in source-space to reveal the neuronal processes that underpin neural plasticity.

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Section: Discussionsupporting

confidence: 90%

Upregulation of cortico-cerebellar functional connectivity after motor learning

et al. 2016

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“…Moreover, stimulating simple spike activity of Purkinje cells either pharmacologically or optogenetically leads to an increase in the excitatory phase of the modulation amplitude of the simple spikes as well as an increase in the gain of compensatory eye movements (van der Steen and Tan 1997;De Zeeuw et al 2004;Nguyen-Vu et al 2013). Thus, in line with the data obtained by Wang and colleagues (2011) , which in turn innervate the oculomotor neurons (OMs) driving the eyes to the opposite side.…”

Section: Motor Learning In a Zebrin-positive Module: Adaptation Of Thsupporting

confidence: 68%

Motor Learning and the Cerebellum

Zeeuw

Brinke²

2015

Cold Spring Harb Perspect Biol

202

168

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Although our ability to store semantic declarative information can nowadays be readily surpassed by that of simple personal computers, our ability to learn and express procedural memories still outperforms that of supercomputers controlling the most advanced robots. To a large extent, our procedural memories are formed in the cerebellum, which embodies more than two-thirds of all neurons in our brain. In this review, we will focus on the emerging view that different modules of the cerebellum use different encoding schemes to form and express their respective memories. More specifically, zebrin-positive zones in the cerebellum, such as those controlling adaptation of the vestibulo-ocular reflex, appear to predominantly form their memories by potentiation mechanisms and express their memories via rate coding, whereas zebrin-negative zones, such as those controlling eyeblink conditioning, appear to predominantly form their memories by suppression mechanisms and express their memories in part by temporal coding using rebound bursting. Together, the different types of modules offer a rich repertoire to acquire and control sensorimotor processes with specific challenges in the spatiotemporal domain.

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“…The CAG promoter as well as other ubiquitous promoters, such as cytomegalovirus or elongation factor-1α promoter, have been used for AAV-mediated transduction of cerebellar Purkinje cells (Broekman et al, 2006;Kaemmerer et al, 2000;Kaneko et al, 2011;Najafi et al, 2014;Nguyen-Vu et al, 2013;Xia et al, 2004). Consistently, we also confirmed that AAV1 with the CAG promoter (AAV1-CAG) successfully drove GFP expression in Purkinje cells of adult mice, which were visualized by staining with a calbindin antibody ( Fig.…”

Section: Broad Expression Patterns Of Transgenes Driven By the Cag Orsupporting

confidence: 80%

“…Viral vectormediated gene delivery in Purkinje cells has been performed in various research on neurodegenerative disorders as well as Purkinje cell development or function (Alisky et al, 2000;Broekman et al, 2006;Gibson et al, 2014;Kaemmerer et al, 2000;Kaneko et al, 2011;Najafi et al, 2014;Nguyen-Vu et al, 2013;Takayama et al, 2008;Torashima et al, 2006;Tsubota et al, 2011;Xia et al, 2004). Several serotypes of AAV were also tested, and expression of the transgene in Purkinje cells was observed using AAV serotype 1 (AAV1), 2, 5, or 8 (Hirai, 2008).…”

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confidence: 99%