2017年3月10日，国际sci神经科学期刊《Cerebral Cortex》在线发表了复旦大学脑科学研究院张嘉漪课题组题为“Reciprocal connections between cortex and thalamus contribute to retinal axon targeting to dorsal lateral geniculate nucleus”。刁玉璞和崔利园为该论文的共同第一作者，脑科学研究院张嘉漪研究员为论文的通讯作者。

视网膜-外膝体-视皮层是主要的成像视觉环路，其中背部外膝体和视皮层间具有相互连接，负责处理精确的视觉信息。已有证据表明，在发育过程中，背部外膝体和视皮层间的投射通过相互作用形成精确的视觉环路。然而，视网膜与背部外膝体形成连接的机制并不清楚。

研究发现视皮层和背部外膝体间的相互连接是介导视网膜到外膝体投射的关键因素，Tra2b条件性敲除小鼠(Tra2b-flox；Emx1-Cre)在发育早期表现出明显的皮层缺失现象，成年后小鼠的大部分皮层和海马都消失。研究表明，Tra2b条件性敲除小鼠的视网膜到背部外膝体的投射在E18.5出现明显的缺陷，视皮层和背部外膝体间的连接消失，同时在外膝体中和背部外膝体到视皮层的通路上均发现细胞凋亡的现象。在体电生理实验显示，Tra2b条件性敲除小鼠的背部外膝体细胞不具有光反应，确定视网膜到背部外膝体投射的缺陷。通过go-no go的行为实验，我们发现Tra2b条件性敲除小鼠对方向性视觉线索的判断能力比正常小鼠差，提示视网膜到背部外膝体的投射发生缺陷后，小鼠的视觉能力受到影响。为证实视皮层和外膝体间的连接影响视网膜到背部外膝体的投射，我们进一步利用化学损伤和另一条件性敲除小鼠(Fezf2-flox；Emx1-Cre)模型，确定了视网膜到背部外膝体的投射依赖于视网膜和背部外膝体间的连接。有意思的是，在三个小鼠模型中，视网膜到腹侧外膝体和上丘的投射都正常，这是由于腹侧外膝体和上丘都不和视皮层发生直接的投射关系。该研究为视网膜-外膝体-视皮层环路的协调性发育提供了启示性的证据。

原文摘要：The dorsal Lateral Geniculate Nucleus (dLGN) is the primary image-forming target of the retina and shares a reciprocal connection with primary visual cortex (V1). Previous studies showed that corticothalamic input is essential for the development of thalamocortical projections， but less is known about the potential role of this reciprocal connection in the development of retinal projections. Here， we show a deficit of retinal innervation in the dLGN around E18.5 in Tra2β conditional knockout (cKO) “cortexless” mice， an age when apoptosis occurs along the thalamocortical tract and in some dLGN neurons. In vivo electrophysiology experiments in the dLGN further confirmed the loss of functional retinal input. Experiments with N-methyl-d-aspartic acid-induced V1 lesion as well as Fezf2 cKO mice confirmed that the disruption of connections between the dLGN and V1 lead to abnormal retinal projections to the dLGN. Interestingly， retinal projections to the ventral Lateral Geniculate Nucleus (vLGN) and Superior Colliculus (SC) were normal in all 3 mice models. Finally， we show that the cortexless mice had worse performance than control mice in a go-no go task with visual cues. Our results provide evidence that the wiring of visual circuit from the retina to the dLGN and V1 thereafter is coordinated at a surprisingly early stage of circuit development.