Establishment of functional synaptic connections in a selective manner is essential for nervous system operation. In mammalian retinas, rod and cone photoreceptors form selective synaptic connections with different classes of bipolar cells (BCs) to propagate light signals. While there has been progress in elucidating rod wiring, molecular mechanisms used by cones to establish functional synapses with BCs have remained unknown. Using an unbiased proteomic strategy in cone-dominant species, we identified the cell-adhesion molecule ELFN2 to be pivotal for the functional wiring of cones with the ON type of BC. It is selectively expressed in cones and transsynaptically recruits the key neurotransmitter receptor mGluR6 in ON-BCs to enable synaptic transmission. Remarkably, ELFN2 in cone terminals functions in synergy with a related adhesion molecule, ELFN1, and their concerted interplay during development specifies selective wiring and transmission of cone signals. These findings identify a synaptic connectivity mechanism of cones and illustrate how interplay between adhesion molecules and postsynaptic transmitter receptors orchestrates functional synaptic specification in a neural circuit.

以选择性方式建立功能性突触连接对于神经系统操作至关重要。在哺乳动物的视网膜中，视杆和视锥光感受器与不同类型的双极细胞（BCs）形成选择性的突触连接，以传播光信号。尽管阐明杆的布线方面已有进展，但视锥细胞与BCs建立功能性突触的分子机制仍然未知。在锥占主导地位的物种中使用无偏蛋白质组学策略，我们确定细胞粘附分子ELFN2对于BC的ON类型的锥的功能性接线至关重要。它在视锥细胞中选择性表达，并在ON-BCs中突触募集关键的神经递质受体mGluR6，以实现突触传递。值得注意的是，锥形末端的ELFN2与相关的粘附分子协同作用，ELFN1及其在开发过程中的协同作用规定了锥体信号的选择性布线和传输。这些发现确定了锥体的突触连接机制，并说明了粘附分子和突触后递质受体之间的相互作用如何协调神经回路中的功能性突触规格。