Abstract
The brain generates predictive motor commands to control the spatiotemporal precision of high-velocity movements. Yet, how the brain organizes automated internal feedback to coordinate the kinematics of such fast movements is unclear. Here we unveil a unique nucleo-olivary loop in the cerebellum and its involvement in coordinating high-velocity movements. Activating the excitatory nucleo-olivary pathway induces well-timed internal feedback complex spike signals in Purkinje cells to shape cerebellar outputs. Anatomical tracing reveals extensive axonal collaterals from the excitatory nucleo-olivary neurons to downstream motor regions, supporting integration of motor output and internal feedback signals within the cerebellum. This pathway directly drives saccades and head movements with a converging direction, while curtailing their amplitude and velocity via the powerful internal feedback mechanism. Our finding challenges the long-standing dogma that the cerebellum inhibits the inferior olivary pathway and provides a new circuit mechanism for the cerebellar control of high-velocity movements.
| Original language | English |
|---|---|
| Pages (from-to) | 1394-1406 |
| Number of pages | 13 |
| Journal | Nature Neuroscience |
| Volume | 26 |
| Issue number | 8 |
| Early online date | 20 Jul 2023 |
| DOIs | |
| Publication status | Published - Aug 2023 |
Bibliographical note
Funding Information:We thank E. Sabel-Goedknegt (Erasmus MC) for assisting with the histological experiments; M. Rutteman (Erasmus MC) for managing animals; E. Haasdijk (Erasmus MC) for assisting with the electron microscopy; C. Schäfer (Erasmus MC) for assisting the patch-clamp recordings; W. Choi and S.B. Paik (Korea Advanced Institute of Science and Technology) for help with the anatomical analysis; P. Isope (CNRS, University of Strasbourg), J. Zhu (Nanjing University), T. Ruigrok (Erasmus MC), D. Jaarsma (Erasmus MC) and C. De Zeeuw (Erasmus MC) for advising and commenting on the manuscript. This work is dedicated to J. (Jerry) I. Simpson for his inspiring discussions when conceiving the study. This work is supported by the NWO VIDI grant (VI.Vidi.192.008 to Z.G.), NWO-Klein grant (OCENW.KLEIN.007 to Z.G.), ERC-stg grant (852869 to Z.G.), National Science and Technology Innovation 2030 Major Program (STI2030-Major Projects, 2022ZD0204800 to Y.Y.), Chinese Academy of Medical Science Innovation Fund for Medical Science (2019-I2M-5-014 to H.G.) and NSFC grant (32192412 to H.G. and T2122015 to A.L.).
Funding Information:
We thank E. Sabel-Goedknegt (Erasmus MC) for assisting with the histological experiments; M. Rutteman (Erasmus MC) for managing animals; E. Haasdijk (Erasmus MC) for assisting with the electron microscopy; C. Schäfer (Erasmus MC) for assisting the patch-clamp recordings; W. Choi and S.B. Paik (Korea Advanced Institute of Science and Technology) for help with the anatomical analysis; P. Isope (CNRS, University of Strasbourg), J. Zhu (Nanjing University), T. Ruigrok (Erasmus MC), D. Jaarsma (Erasmus MC) and C. De Zeeuw (Erasmus MC) for advising and commenting on the manuscript. This work is dedicated to J. (Jerry) I. Simpson for his inspiring discussions when conceiving the study. This work is supported by the NWO VIDI grant (VI.Vidi.192.008 to Z.G.), NWO-Klein grant (OCENW.KLEIN.007 to Z.G.), ERC-stg grant (852869 to Z.G.), National Science and Technology Innovation 2030 Major Program (STI2030-Major Projects, 2022ZD0204800 to Y.Y.), Chinese Academy of Medical Science Innovation Fund for Medical Science (2019-I2M-5-014 to H.G.) and NSFC grant (32192412 to H.G. and T2122015 to A.L.).
Publisher Copyright:
© 2023, The Author(s).