Paul Maëla A, Sigoillot Séverine M, Marti Léa, Urra Quiroz Francisco J, Delagrange Marine, Cheung Hiu W, Martinelli David C, Oriol Elie, Hakim Vincent, Mailly Philippe, Selimi Fekrije
Center for Interdisciplinary Research in Biology (CIRB), Collège de France, Université PSL, CNRS, INSERM, Paris, France.
Inovarion, Paris, France.
Nat Neurosci. 2025 Feb;28(2):308-319. doi: 10.1038/s41593-024-01826-w. Epub 2024 Dec 10.
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.
脑功能依赖于大量形态和功能各异但具有特异性的神经元突触的形成。我们在此表明,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,它是C1q蛋白家族的成员,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的一种输入——下橄榄核神经元中进一步发展,伴随着突触前分泌蛋白C1QL1、CRTAC1和LGI2的额外表达。这些分子协同作用,确定浦肯野细胞靶点上成熟的连接模式。这些结果表明,一些输入会主动并逐渐确定其突触分子身份,而其他输入则依赖于“原始分子编码”。因此,兴奋性突触的分子特异性对于正常的神经回路功能至关重要,它在小鼠出生后的发育过程中逐步获得,并遵循输入特异性规则。