Experience-dependent plasticity in the adult visual cortex is enhanced by locomotion, a process mediated by vasoactive intestinal peptide (VIP)-expressing interneurons. While VIP interneurons are known to signal through both Gamma-aminobutyric acid (GABA) and VIP peptide, the specific contributions of these pathways during different forms of plasticity remain unclear. Monocular deprivation (MD) in adult mice alters cortical responses, though more slowly and differently than during a critical period in early life. Here, we used two-photon calcium imaging in awake adult mice to dissect the roles of VIP and GABA release from VIP interneurons during adult MD and subsequent binocular recovery. We found comparable level of ocular dominance shifts after MD in mice deficient in either peptidergic or GABA signaling, but disrupting GABA signaling impaired recovery of binocular responses. We also showed that running preferentially enhances contralateral eye responses in binocular primary visual cortex. However, this eye-specific modulation of visual responses by running was altered during recovery from MD and was dependent on VIP signaling pathways. These findings highlight the GABA-mediated inhibition by VIP interneurons as a critical pathway for promoting visual restoration in the adult brain.

Significance statement: Using longitudinal two-photon imaging in awake adult mice with genetically altered signaling path-ways in VIP interneurons, we demonstrate that GABAergic, but not peptidergic, signaling from VIP interneurons is essential for the recovery of binocular vision following monocular deprivation. We further reveal that locomotion modulates cortical responses in an eye-specific manner, a property dynamically reshaped by plasticity and dependent on VIP interneuron function. These findings identify a discrete inhibitory circuit element that links behavioral state to sensory recovery and highlight GABA release from VIP cells as a potential therapeutic target for restoring visual function in adulthood.

成年视觉皮层中，经验依赖的可塑性在运动时会增强，这一过程由血管活性肠肽（VIP）表达中间神经元介导。虽然已知VIP中间神经元通过γ-氨基丁酸（GABA）和VIP肽传递信号，但这些通路在不同类型可塑性中的具体作用仍不清楚。成年小鼠单眼剥夺（MD）会改变皮层反应，尽管比生命早期关键期时的改变更慢且不同。在这里，我们使用两光子钙成像技术，在清醒成年小鼠中剖析了VIP和GABA从VIP中间神经元释放对成人MD及随后双眼恢复的作用。我们发现，在缺乏肽类或GABA信号的小鼠中，眼优势位移后的水平相当，但破坏GABA信号会损害双眼反应的恢复。此外，我们还展示了跑步更倾向于增强双眼中枢视觉皮层中的对侧眼反应。然而，在从MD恢复期间，跑步对双眼视觉反应的眼特异性调节发生了改变，并且依赖于VIP信号通路。这些发现突出了由VIP中间神经元介导的GABA抑制作为促进成年大脑视觉恢复的关键路径。

意义声明： 通过在具有遗传性修饰信号通路的清醒成年小鼠中进行纵向两光子成像，我们证明了从VIP中间神经元释放的GABAergic（但不是肽类）信号对单眼剥夺后双眼视觉恢复至关重要。此外，我们揭示了运动以一种眼特异性的方式调节皮层反应，并且这种性质在可塑性动态重塑过程中依赖于VIP中间神经元功能。这些发现确定了一个特定的抑制回路元件，它将行为状态与感觉恢复联系起来，并强调了从VIP细胞释放GABA作为成人期视觉功能恢复潜在治疗目标的重要性。