PDE10A identified by cross-hemisphere visual cortex proteomics restores adult ocular dominance plasticity involving cAMP/CREB signaling

Ocular dominance plasticity (ODP) is robust during the critical period but is restricted in adulthood. The molecular programs that distinguish this permissive state and whether they can be pharmacologically engaged in adulthood remain unclear. Here, using quantitative proteomics of the left and right visual cortices from monocularly deprived (MD) juvenile mice, we identify phosphodiesterase 10 A (PDE10A) and the cAMP signaling pathway as molecular signatures of juvenile ODP. Juvenile MD is associated with reduced PDE10A and increased phosphorylated CREB (pCREB) in the visual cortex contralateral to the deprived eye, whereas adult mice show no comparable response. In adult mice, systemic administration of the selective PDE10A inhibitor TAK-063 during MD reinstates an experience-dependent ocular dominance shift and reduces visual acuity in the deprived eye. This is accompanied by increased cortical cAMP and pPKA, an inverted-U pCREB response peaking at 0.3 mg/kg, and upregulation of plasticity-related synaptic proteins. TAK-063 does not alter basal visual function, retinal electrophysiology, or locomotor behavior in non-deprived adults, excluding nonspecific sensory/motor confounds. These findings identify PDE10A as a candidate molecular regulator of visual cortical plasticity and support its pharmacological inhibition as a strategy to facilitate experience-dependent plasticity in the adult visual cortex.