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      Disrupting cortico-cerebellar communication impairs dexterity

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          Abstract

          To control reaching, the nervous system must generate large changes in muscle activation to drive the limb toward the target, and must also make smaller adjustments for precise and accurate behavior. Motor cortex controls the arm through projections to diverse targets across the central nervous system, but it has been challenging to identify the roles of cortical projections to specific targets. Here, we selectively disrupt cortico-cerebellar communication in the mouse by optogenetically stimulating the pontine nuclei in a cued reaching task. This perturbation did not typically block movement initiation, but degraded the precision, accuracy, duration, or success rate of the movement. Correspondingly, cerebellar and cortical activity during movement were largely preserved, but differences in hand velocity between control and stimulation conditions predicted from neural activity were correlated with observed velocity differences. These results suggest that while the total output of motor cortex drives reaching, the cortico-cerebellar loop makes small adjustments that contribute to the successful execution of this dexterous movement.

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          Most cited references69

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            DeepLabCut: markerless pose estimation of user-defined body parts with deep learning

            Quantifying behavior is crucial for many applications in neuroscience. Videography provides easy methods for the observation and recording of animal behavior in diverse settings, yet extracting particular aspects of a behavior for further analysis can be highly time consuming. In motor control studies, humans or other animals are often marked with reflective markers to assist with computer-based tracking, but markers are intrusive, and the number and location of the markers must be determined a priori. Here we present an efficient method for markerless pose estimation based on transfer learning with deep neural networks that achieves excellent results with minimal training data. We demonstrate the versatility of this framework by tracking various body parts in multiple species across a broad collection of behaviors. Remarkably, even when only a small number of frames are labeled (~200), the algorithm achieves excellent tracking performance on test frames that is comparable to human accuracy.
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              Fully integrated silicon probes for high-density recording of neural activity

              Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca2+ imaging offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials. Until now, no technology compatible with use in unrestrained animals has combined high spatiotemporal resolution with large volume coverage. Here we design, fabricate and test a new silicon probe known as Neuropixels to meet this need. Each probe has 384 recording channels that can programmably address 960 complementary metal–oxide–semiconductor (CMOS) processing-compatible low-impedance TiN sites that tile a single 10-mm long, 70 × 20-μm cross-section shank. The 6 × 9-mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed and digitized on the base, allowing the direct transmission of noise-free digital data from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were recorded simultaneously from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed large populations of neurons from several brain structures to be recorded in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens a path towards recording of brain-wide neural activity during behaviour.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                29 July 2021
                2021
                : 10
                : e65906
                Affiliations
                [1 ]Janelia Research Campus AshburnUnited States
                [2 ]Johns Hopkins University BaltimoreUnited States
                [3 ]Italian Institute of Technology GenoaItaly
                Champalimaud Foundation Portugal
                Stanford University United States
                Champalimaud Foundation Portugal
                Author notes
                [†]

                These authors contributed equally to this work.

                [‡]

                These authors also contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-5836-5921
                https://orcid.org/0000-0003-3386-3243
                https://orcid.org/0000-0003-4961-222X
                https://orcid.org/0000-0002-8448-9143
                https://orcid.org/0000-0002-1489-7758
                https://orcid.org/0000-0002-6563-1423
                Article
                65906
                10.7554/eLife.65906
                8321550
                34324417
                9388f702-37c3-4b68-8d5f-34c4ad3ecce2
                © 2021, Guo et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 18 December 2020
                : 28 June 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000011, Howard Hughes Medical Institute;
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Neuroscience
                Custom metadata
                The flow of neural activity across the cortico-cerebellar loop enables mice to reach for objects with skill and precision.

                Life sciences
                motor cortex,cerebellum,pontine nuclei,neural dynamics,dexterity,reaching,mouse
                Life sciences
                motor cortex, cerebellum, pontine nuclei, neural dynamics, dexterity, reaching, mouse

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