C1ql3 promotes cognitive flexibility behavior in mice.

Cognitive flexibility, the ability to adapt behavioral strategies based on changing circumstances, is deficient in patients with certain neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia. Cognitive flexibility can be measured in humans and animal models using attentional set-shifting tasks, which require activity of the prefrontal cortex (PFC) and other key brain regions. We demonstrate that C1QL3, a protein involved in regulating excitatory synapse density in the PFC and other brain circuits, is important for attentional set-shifting, using a mouse model of C1ql3 disruption. Conditional deletion of C1ql3 from neurons specifically in the PFC of adult mice was not sufficient to impair attentional set-shifting behavior, highlighting the potential role of C1ql3 in promoting cognitive flexibility through expression in other key brain circuits and/or neurodevelopmental processes.