The choroid plexus (ChP) regulates cerebrospinal fluid (CSF) composition, providing essential molecular cues for brain development. Apocrine secretion by embryonic ChP epithelial cells is a key regulator of the CSF proteome and neurodevelopment in male and female mice. Activation of serotonergic 5-HT2C receptors triggers sustained calcium signaling, driving high-volume apocrine secretion in mouse and human ChP. This secretion alters the CSF proteome, stimulating neural progenitors and shifting their developmental trajectory. Inducing ChP secretion in utero disrupts neural progenitor dynamics, cerebral cortical architecture, and offspring behavior. Illness or lysergic acid diethylamide exposure during pregnancy provokes coordinated ChP secretion in mouse embryos. The findings reveal a fundamental secretory pathway in the ChP that shapes brain development, and its disruption can have lasting consequences for brain health.
A single dose of psilocybin enhances behavioral flexibility by altering neural activity in the retrosplenial cortex. Using longitudinal single-cell calcium imaging in mice during a 5-day trace fear learning and extinction assay, the study found that psilocybin suppressed fear-active neurons and recruited extinction-active neurons, a pattern that predicted improved fear extinction. A computational model showed that inhibiting simulated fear-active units modulated the recruitment of extinction-active units and behavioral variability in freezing, consistent with the experimental findings. These results suggest psilocybin promotes behavioral flexibility by reorganizing cortical ensembles in the retrosplenial cortex.