Interactions between excitatory neurons and parvalbumin interneurons in V1 underlie neural mechanisms of amblyopia and visual stimulation treatment.

As the main cause of visual function deficits in children and adolescents worldwide, amblyopia causes serious impairment of monocular visual acuity and stereopsis. The recovery of visual functions from amblyopia beyond the critical period is slow and incomplete due to the limited plasticity of the mature cortex; notably, visual stimulation training seems to be an effective therapeutic strategy in clinical practice. However, the precise neural basis and cellular mechanisms that underlie amblyopia and visual stimulation treatment remain to be elucidated. Using monocular deprivation in juvenile mice to model amblyopia, we employed two-photon calcium imaging and chemogenetic techniques to investigate the visual responses of individual excitatory neurons and parvalbumin (PV(+)) interneurons in the primary visual cortex (V1) of amblyopic mice. We demonstrate that amblyopic mice exhibit an excitation/inhibition (E/I) imbalance. Moreover, visual stimulation decreases the response of PV(+) interneurons, reactivates the ocular dominance plasticity of excitatory neurons, and promotes vision recovery in adult amblyopic mice. Our results reveal a dynamic E/I balance between excitatory neurons and PV(+) interneurons that may underlie the neural mechanisms of amblyopia during cortical development and visual stimulation-mediated functional recovery from adult amblyopia, providing evidence for therapeutic applications that rely on reactivating adult cortical plasticity.