Planar cell polarity protein Celsr2 maintains structural and functional integrity of adult cortical synapses

Prog Neurobiol. 2022 Dec:219:102352. doi: 10.1016/j.pneurobio.2022.102352. Epub 2022 Sep 8.

Abstract

A few developmental genes remain persistently expressed in the adult stage, whilst their potential functions in the mature brain remain underappreciated. Here, we report the unexpected importance of Celsr2, a core Planar cell polarity (PCP) component, in maintaining the structural and functional integrity of adult neocortex. Celsr2 is highly expressed during development and remains expressed in adult neocortex. In vivo synaptic imaging in Celsr2 deficient mice revealed alterations in spinogenesis and reduced neuronal calcium activities, which are associated with impaired motor learning. These phenotypes were accompanied with anomalies of both postsynaptic organization and presynaptic vesicles. Knockout of Celsr2 in adult mice recapitulated those features, further supporting the role of Celsr2 in maintaining the integrity of mature cortex. In sum, our data identify previously unrecognized roles of Celsr2 in the maintenance of synaptic function and motor learning in adulthood.

Keywords: Corticostriatal circuit; Motor learning; Pla2g4e; Synaptic plasticity; de novo spinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain
  • Cadherins
  • Cell Polarity*
  • Mice
  • Mice, Knockout
  • Neuronal Plasticity / physiology
  • Neurons
  • Synapses* / physiology

Substances

  • Celsr2 protein, mouse
  • Cadherins