法国巴黎文理大学Fekrije Selimi团队揭示了，小脑浦肯野细胞上兴奋性突触多样性的逐步分子特化。这一研究成果于2024年12月10日在线发表在国际学术期刊《自然—神经科学》上。

研究人员展示了在小鼠中，小脑浦肯野细胞上突触的初步形成涉及一种突触前蛋白——CBLN1。这是一种C1q蛋白家族成员，由所有类型的兴奋性输入分泌。随后，分子程序仅在浦肯野细胞的一个输入——下橄榄核神经元中演化，并伴随突触前分泌蛋白C1QL1、CRTAC1和LGI2的表达。这些分子协同工作，指定浦肯野细胞靶标上的成熟连接模式。

这些结果表明，一些输入会主动并逐步指定它们的突触分子身份，而另一些则依赖于“原始分子代码”。因此，兴奋性突触的分子特化，对于正确的回路功能至关重要，这是在小鼠出生后发育过程中逐步获得的，并遵循输入特异性的规则。

附：英文原文

Title: Stepwise molecular specification of excitatory synapse diversity onto cerebellar Purkinje cells

Author: Paul, Mala A., Sigoillot, Sverine M., Marti, La, Urra Quiroz, Francisco J., Delagrange, Marine, Cheung, Hiu W., Martinelli, David C., Oriol, Elie, Hakim, Vincent, Mailly, Philippe, Selimi, Fekrije

Issue&Volume: 2024-12-10

Abstract: 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.

DOI: 10.1038/s41593-024-01826-w

Source: https://www.nature.com/articles/s41593-024-01826-w