Critical periods (CPs) are time windows of heightened brain plasticity during which experience refines synaptic connections to achieve mature functionality. At glutamatergic synapses on dendritic spines of principal cortical neurons, the maturation is largely governed by postsynaptic density protein-95 (PSD-95)-dependent synaptic incorporation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors into nascent AMPA-receptor silent synapses. Consequently, in mouse primary visual cortex (V1), impaired silent synapse maturation in PSD-95-deficient neurons prevents the closure of the CP for juvenile ocular dominance plasticity (jODP). A structural hallmark of jODP is increased spine elimination, induced by brief monocular deprivation (MD). However, it is unknown whether impaired silent synapse maturation facilitates spine elimination and also preserves juvenile structural plasticity. Using two-photon microscopy, we assessed spine dynamics in apical dendrites of layer 2/3 pyramidal neurons (PNs) in binocular V1 during ODP in awake adult mice. Under basal conditions, spine formation and elimination ratios were similar between PSD-95 knockout (KO) and wild-type (WT) mice. However, a brief MD affected spine dynamics only in KO mice, where MD doubled spine elimination, primarily affecting newly formed spines, and caused a net reduction in spine density similar to what has been observed during jODP in WT mice. A similar increase in spine elimination after MD occurred if PSD-95 was knocked down in single PNs of layer 2/3. Thus, structural plasticity is dictated cell autonomously by PSD-95 in vivo in awake mice. Loss of PSD-95 preserves hallmark features of spine dynamics in jODP into adulthood, revealing a functional link of PSD-95 for experience-dependent synapse maturation and stabilization during CPs.

关键期（CP）是大脑可塑性增强的时间窗口，在此期间经验会完善突触连接以实现成熟的功能。在主要皮层神经元树突棘上的谷氨酸突触，成熟很大程度上受突触后密度蛋白 95 (PSD-95) 依赖性突触掺入 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 控制。 ) 受体进入新生的 AMPA 受体沉默突触。因此，在小鼠初级视觉皮层 (V1) 中，PSD-95 缺陷神经元中沉默突触成熟受损会阻止幼年眼优势可塑性 (jODP) 的 CP 关闭。 jODP 的一个结构特征是由短暂的单眼剥夺 (MD) 引起的脊柱消除增加。然而，尚不清楚沉默突触成熟受损是否有利于刺的消除并保留幼年的结构可塑性。使用双光子显微镜，我们评估了清醒成年小鼠 ODP 期间双眼 V1 中 2/3 层锥体神经元 (PN) 顶端树突的脊柱动力学。在基础条件下，PSD-95 敲除 (KO) 和野生型 (WT) 小鼠之间的脊柱形成和消除比率相似。然而，短暂的 MD 仅影响 KO 小鼠的脊柱动态，其中 MD 使脊柱消除加倍，主要影响新形成的脊柱，并导致脊柱密度的净减少，类似于 WT 小鼠中 jODP 期间观察到的情况。如果 PSD-95 在第 2/3 层的单个 PN 中被击倒，MD 后脊柱消除也会出现类似的增加。因此，在清醒小鼠体内，结构可塑性是由 PSD-95 自主决定的。 PSD-95 的缺失保留了 jODP 到成年期脊柱动力学的标志性特征，揭示了 PSD-95 在 CP 期间与经验依赖的突触成熟和稳定的功能联系。