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

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.

Celsr2 regulates NMDA receptors and dendritic homeostasis in dorsal CA1 to enable social memory.

Social recognition and memory are critical for survival. The hippocampus serves as a central neural substrate underlying the dynamic coding and transmission of social information. Yet the molecular mechanisms regulating social memory integrity in hippocampus remain unelucidated. Here we report unexpected roles of Celsr2, an atypical cadherin, in regulating hippocampal synaptic plasticity and social memory in mice. Celsr2-deficient mice exhibited defective social memory, with rather intact levels of sociability. In vivo fiber photometry recordings disclosed decreased neural activity of dorsal CA1 pyramidal neuron in Celsr2 mutants performing social memory task. Celsr2 deficiency led to selective impairment in NMDAR but not AMPAR-mediated synaptic transmission, and to neuronal hypoactivity in dorsal CA1. Those activity changes were accompanied with exuberant apical dendrites and immaturity of spines of CA1 pyramidal neurons. Strikingly, knockdown of Celsr2 in adult hippocampus recapitulated the behavioral and cellular changes observed in knockout mice. Restoring NMDAR transmission or CA1 neuronal activities rescued social memory deficits. Collectively, these results show a critical role of Celsr2 in orchestrating dorsal hippocampal NMDAR function, dendritic and spine homeostasis, and social memory in adulthood.