The defining features of a neuron are its functional and anatomical connections with thousands of other neurons in the brain. Together, these neurons form functional networks that direct animal behavior. Current approaches that allow the interrogation of specific populations of neurons and neural circuits rely heavily on targeting their gene expression profiles or connectivity. However, these approaches are often unable to delineate specific neuronal populations. Here, we developed a novel intersectional split intein-mediated split-Cre recombinase system that can selectively label specific types of neurons based on their gene expression profiles and structural connectivity. We developed this system by splitting Cre recombinase into two fragments with evolved split inteins and subsequently expressed one fragment under the influence of a cell type-specific promoter in a transgenic animal, and delivered the other fragment via retrograde viral gene transfer. This approach results in the reconstitution of Cre recombinase in only specific population of neurons projecting from a specific brain region or in those of a specific neuronal type. Taken together, our split intein-based split-Cre system will be useful for sophisticated characterization of mammalian brain circuits.

中文翻译：

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使用新型交叉分裂内含肽介导的分裂-Cre 重组酶系统的神经回路分析。

神经元的定义特征是它与大脑中数千个其他神经元的功能和解剖学连接。这些神经元共同形成了指导动物行为的功能网络。当前允许询问特定神经元和神经回路群的方法在很大程度上依赖于针对它们的基因表达谱或连接性。然而，这些方法通常无法描绘特定的神经元群。在这里，我们开发了一种新的交叉分裂内含肽介导的分裂 Cre 重组酶系统，可以根据特定类型的神经元的基因表达谱和结构连接选择性地标记它们。我们通过将 Cre 重组酶分裂成两个带有进化分裂内含肽的片段来开发这个系统，随后在转基因动物中细胞类型特异性启动子的影响下表达一个片段，并通过逆行病毒基因转移传递另一个片段。这种方法导致 Cre 重组酶仅在从特定大脑区域或特定神经元类型突出的特定神经元群中重建。综上所述，我们基于内含肽的 split-Cre 系统将有助于哺乳动物大脑回路的复杂表征。这种方法导致 Cre 重组酶仅在从特定大脑区域或特定神经元类型突出的特定神经元群中重建。综上所述，我们基于内含肽的 split-Cre 系统将有助于哺乳动物大脑回路的复杂表征。这种方法导致 Cre 重组酶仅在从特定大脑区域或特定神经元类型突出的特定神经元群中重建。综上所述，我们基于内含肽的 split-Cre 系统将有助于哺乳动物大脑回路的复杂表征。