Brain function relies on the generation of a large variety of morphologically and functionally diverse, but specific, neuronal synapses. Here we show that, in mice, the initial formation of synapses on cerebellar Purkinje cells involves a presynaptic protein—CBLN1, a member of the C1q protein family—that is secreted by all types of excitatory inputs. The molecular program then evolves only in one of the Purkinje cell inputs, the inferior olivary neurons, with the additional expression of the presynaptic secreted proteins C1QL1, CRTAC1 and LGI2. These molecules work in concert to specify the mature connectivity pattern on the Purkinje cell target. These results show that some inputs actively and gradually specify their synaptic molecular identity, while others rely on the ‘original molecular code’. Thus, the molecular specification of excitatory synapses, crucial for proper circuit function, is acquired in a stepwise manner during mouse postnatal development and obeys input-specific rules.

大脑功能依赖于各种形态和功能多样但特异性的神经元突触的产生。在这里，我们表明，在小鼠中，小脑浦肯野细胞上突触的初始形成涉及一种突触前蛋白——CBLN1，C1q 蛋白家族的一员——它由所有类型的兴奋性输入分泌。然后，分子程序仅在浦肯野细胞输入之一，即下橄榄神经元中进化，突触前分泌蛋白 C1QL1、CRTAC1 和 LGI2 的额外表达。这些分子协同工作，以指定浦肯野细胞靶标上的成熟连接模式。这些结果表明，一些输入主动并逐渐指定它们的突触分子身份，而另一些则依赖于“原始分子密码”。因此，兴奋性突触的分子规格对正常的电路功能至关重要，在小鼠出生后发育过程中以逐步方式获得，并遵守输入特定的规则。