Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity

• Otx2 homeoprotein secreted by the choroid plexus is conveyed to cortical PV cells
• Otx2 knockdown in the choroid plexus reduces local cortical content
• Reducing Otx2 PV cell content reactivates plasticity in the adult visual cortex
• Amblyopia can be cured in adult mice by knocking down Otx2 in the choroid plexus

SummaryBrain plasticity is often restricted to critical periods in early life. Here, we show that a key regulator of this process in the visual cortex, Otx2 homeoprotein, is synthesized and secreted globally from the choroid plexus. Consequently, Otx2 is maintained in selected GABA cells unexpectedly throughout the mature forebrain. Genetic disruption of choroid-expressed Otx2 impacts these distant circuits and in the primary visual cortex reopens binocular plasticity to restore vision in amblyopic mice. The potential to regulate adult cortical plasticity through the choroid plexus underscores the importance of this structure in brain physiology and offers therapeutic approaches to recovery from a broad range of neurodevelopmental disorders.

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