4.7 Article

Synaptic pruning through glial synapse engulfment upon motor learning

期刊

NATURE NEUROSCIENCE
卷 25, 期 11, 页码 1458-+

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NATURE PORTFOLIO
DOI: 10.1038/s41593-022-01184-5

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资金

  1. JSPS KAKENHI [16K18388, 18K06457, 18J00603, 18H05110, 19H03338, 20H05046, 20H05896, 22H02713, ,16H06280, 18H05120, 19K22469, 19H03323]
  2. Naito Foundation
  3. Satoshi Ohmura Foundation
  4. Technical support platforms for promoting research of Advanced Bioimaging Support [JP16H06280]
  5. Opto-Science and Technology
  6. NOVARTIS Foundation
  7. Takeda Science Foundation
  8. Joint Usage/Research Program of Medical Research Institute
  9. AMED under the Brain/MINDS project [JP21dm0207111]
  10. Columbia University Target of Opportunity award

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The study found that motor learning induces synaptic engulfment by cerebellar Bergmann glia (BG), which contributes to synaptic pruning during the improvement of motor adaptation.
Synaptic pruning is a fundamental process of neuronal circuit refinement in learning and memory. Accumulating evidence suggests that glia participates in sculpting the neuronal circuits through synapse engulfment. However, whether glial involvement in synaptic pruning has a role in memory formation remains elusive. Using newly developed phagocytosis reporter mice and three-dimensional ultrastructural characterization, we found that synaptic engulfment by cerebellar Bergmann glia (BG) frequently occurred upon cerebellum-dependent motor learning in mice. We observed increases in pre- and postsynaptic nibbling by BG along with a reduction in spine volume after learning. Pharmacological blockade of engulfment with Annexin V inhibited both the spine volume reduction and overnight improvement of motor adaptation. These results indicate that BG contribute to the refinement of the mature cerebellar cortical circuit through synaptic engulfment during motor learning. Using new phagocytosis reporter mice and 3D ultrastructural characterization, Morizawa et al. show that motor learning induces synaptic engulfment by BG, which contributes to synaptic pruning during the improvement of motor adaptation.

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