bims-climfi 2023-05-07 papers

Issue of 2023–05–07
two papers selected by
Jun Maruta, Mount Sinai Health System

Nat Commun. 2023 May 03. 14(1): 2548

Multidimensional cerebellar computations for flexible kinematic control of movements.

Akshay Markanday, Sungho Hong, Junya Inoue, Erik De Schutter, Peter Thier.

Both the environment and our body keep changing dynamically. Hence, ensuring movement precision requires adaptation to multiple demands occurring simultaneously. Here we show that the cerebellum performs the necessary multi-dimensional computations for the flexible control of different movement parameters depending on the prevailing context. This conclusion is based on the identification of a manifold-like activity in both mossy fibers (MFs, network input) and Purkinje cells (PCs, output), recorded from monkeys performing a saccade task. Unlike MFs, the PC manifolds developed selective representations of individual movement parameters. Error feedback-driven climbing fiber input modulated the PC manifolds to predict specific, error type-dependent changes in subsequent actions. Furthermore, a feed-forward network model that simulated MF-to-PC transformations revealed that amplification and restructuring of the lesser variability in the MF activity is a pivotal circuit mechanism. Therefore, the flexible control of movements by the cerebellum crucially depends on its capacity for multi-dimensional computations.

DOI: https://doi.org/10.1038/s41467-023-37981-0

Cell Rep. 2023 May 03. pii: S2211-1247(23)00440-0. [Epub ahead of print]42(5): 112429

Cerebellar granule cell signaling is indispensable for normal motor performance.

Joon-Hyuk Lee, Mehak M Khan, Amanda P Stark, Soobin Seo, Aliya Norton, Zhiyi Yao, Christopher H Chen, Wade G Regehr.

Within the cerebellar cortex, mossy fibers (MFs) excite granule cells (GCs) that excite Purkinje cells (PCs), which provide outputs to the deep cerebellar nuclei (DCNs). It is well established that PC disruption produces motor deficits such as ataxia. This could arise from either decreases in ongoing PC-DCN inhibition, increases in the variability of PC firing, or disruption of the flow of MF-evoked signals. Remarkably, it is not known whether GCs are essential for normal motor function. Here we address this issue by selectively eliminating calcium channels that mediate transmission (CaV2.1, CaV2.2, and CaV2.3) in a combinatorial manner. We observe profound motor deficits but only when all CaV2 channels are eliminated. In these mice, the baseline rate and variability of PC firing are unaltered, and locomotion-dependent increases in PC firing are eliminated. We conclude that GCs are indispensable for normal motor performance and that disruption of MF-induced signals impairs motor performance.

Keywords: CP: Neuroscience; Purkinje cell; balance beam; calcium channel; cerebellum; gait; granule cell; motor function; rotarod

DOI: https://doi.org/10.1016/j.celrep.2023.112429