Pan Meng, Ye Jingjing, Yan Yijing, Chen Ailin, Li Xinyu, Jiang Xin, Wang Wei, Meng Xin, Chen Shujian, Gu Yu, Shi Xuefeng
Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China.
School of Medicine, Nankai University, Tianjin, China.
Front Cell Neurosci. 2025 Apr 28;19:1574505. doi: 10.3389/fncel.2025.1574505. eCollection 2025.
The visual thalamus serves as a critical hub for feature preprocessing in visual processing pathways. Emerging evidence demonstrates that experience-dependent plasticity can be revealed by monocular deprivation (MD) in the dorsolateral geniculate nucleus (dLGN) of the thalamus. However, whether and how this thalamic plasticity induces changes in multiple receptive field properties and the potential mechanisms remain unclear. Using electrophysiology, here we show that binocular neurons in the dLGN of 4-day MD mice starting at P28 undergo a significant ocular dominance (OD) shift during the critical period. This OD plasticity could be attributed to the potentiation of ipsilateral eye responses but not to the depression of deprived eye responses, contrasting with conventional observations in the primary visual cortex (V1). The direction and orientation selectivity of ipsilateral eye responses, but not of contralateral eye responses in these neurons, were dramatically reduced. Developmental analysis revealed pre-critical and critical period-associated changes in densities of both GABA positive neurons and GABA receptor α1 subunit (GABRA1) positive neurons. However, early compensatory inhibition from V1 feedback in P18 MD mice maintained network stability with no changes in OD and feature selectivity. Mechanistically, pharmacological activation of GABA receptors rescued the MD-induced OD shifts and feature selectivity impairments in critical period MD mice, operating independently of the V1 feedback. Furthermore, under different contrast levels and spatial frequencies, these critical period-associated changes in receptive field properties still indicate alterations in ipsilateral eye responses alone. Together, these findings provide novel insights into the developmental mechanisms of thalamic sensory processing, highlighting the thalamus as an active participant in experience-dependent visual plasticity rather than merely a passive relay station. The identified GABA-mediated plasticity mechanisms offer potential therapeutic targets for visual system disorders.
视觉丘脑是视觉处理通路中进行特征预处理的关键枢纽。新出现的证据表明，丘脑背外侧膝状核（dLGN）中的单眼剥夺（MD）可揭示经验依赖性可塑性。然而，这种丘脑可塑性是否以及如何诱导多个感受野特性的变化以及潜在机制仍不清楚。在此，我们利用电生理学方法表明，从P28开始进行4天MD处理的小鼠dLGN中的双眼神经元在关键期经历了显著的眼优势（OD）转移。这种OD可塑性可归因于同侧眼反应的增强，而非剥夺眼反应的减弱，这与初级视觉皮层（V1）中的传统观察结果形成对比。这些神经元中同侧眼反应的方向和取向选择性显著降低，但对侧眼反应则不然。发育分析揭示了GABA阳性神经元和GABA受体α1亚基（GABRA1）阳性神经元密度在关键期前和关键期相关的变化。然而，P18 MD小鼠中来自V1反馈的早期代偿性抑制维持了网络稳定性，OD和特征选择性均未改变。从机制上讲，GABA受体的药理学激活挽救了关键期MD小鼠中MD诱导的OD转移和特征选择性损伤，且独立于V1反馈起作用。此外，在不同对比度水平和空间频率下，这些与关键期相关的感受野特性变化仍仅表明同侧眼反应的改变。总之，这些发现为丘脑感觉处理的发育机制提供了新的见解，突出了丘脑作为经验依赖性视觉可塑性的积极参与者，而非仅仅是一个被动中继站。所确定的GABA介导的可塑性机制为视觉系统疾病提供了潜在的治疗靶点。
