Sensorimotor plasticity in the cerebellar microcircuit and its therapeutic potential

Projektinformationen

CerebellumTherapy

ID Finanzhilfevereinbarung: 753398

DOI

10.3030/753398

Projekt abgeschlossen

EK-Unterschriftsdatum 23 Februar 2017

Startdatum 1 März 2017

Enddatum 28 Februar 2019

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 195 454,80

EU-Beitrag

€ 195 454,80

Koordiniert durch

UNIVERSITY COLLEGE LONDON
United Kingdom

Periodic Reporting for period 1 - CerebellumTherapy (Sensorimotor plasticity in the cerebellar microcircuit and its therapeutic potential)

Berichtszeitraum: 2017-03-01 bis 2019-02-28

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Summary of the context:
The cerebellum plays a central role in precise motor control, which is governed by climbing fibre inputs to Purkinje cells. Climbing fibres also robustly respond to sensory stimuli in the absence of motor outputs. However, how climbing fibre inputs can provide a link between sensory processing and motor timing remains unknown.

The problem/issue addressed:
Link between sensory and motor function of the cerebellum.

Importance for the society:
Elucidating and manipulating sensorimotor association in the cerebellum could form a novel therapeutic strategy for diseases such as autism spectrum disorder.

Overall objectives:
Revealing and understanding core aspects of cerebellar function.

Conclusions of the action:
Spatiotemporally organised complex spike activity links multi-sensory integration and timed motor initiation.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

Work performed:
Established a multi-sensory timing task. Performed two-photon imaging, optogenetics, and electrical recording in mice during the task. Wrote a manuscript describing the results. Supervised and trained students to do experiments and analysis, and make figures.

Overview of the results:
Optogenetic stimulation of Purkinje cell output from Crus I delays or abolishes sensory-evoked motor responses in the multi-sensory timing task, demonstrating that this region is crucial for this behaviour. Two-photon calcium imaging of climbing fibre responses during the task revealed that their activity contains sensory information that is consistently organised into parasagittal bands. Spatiotemporal activity patterns within individual bands faithfully encode sensorimotor contexts and the temporal precision of motor initiation.

Exploitation and dissemination:
Presented the results in international conferences. Publish in a high impact journal to disseminate the results to broader readership.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

Progress beyond the state of the art:
Established a novel multi-sensory timing task to address circuit mechanisms of sensorimotor association in the cerebellum. Elucidated zonal organisation of cerebellar sensorimotor function which is highly consistent across individuals. Discovered that spatiotemporally organised zonal complex spike activity links multi-sensory integration and timed motor initiation.

Potential impacts:
Provide a new perspective on cerebellar function which could be reflected on a novel strategy to treat diseases such as autism spectrum disorder.

Summary schematics for the main findings of this project.