Morphology, physiology and connectivity of genetically specified VIP neurons in mouse barrel cortex

小鼠桶状皮质中基因指定的 VIP 神经元的形态学、生理学和连接性

• 批准号: 496423149
• 负责人: Professor Dr. Jochen Ferdinand Staiger
• 金额: --
• 依托单位: Institut für Neuroanatomie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/496423149?language=en
• 关键词: Morphology; physiology; connectivity; genetically; specified

Genetic access via Cre-driver lines have made vasoactive intestinal polypeptide (VIP) expressing neurons a subject of major discoveries, like for instance their brain-wide signaling of reward or punishment in the context of learning. Also an abundant disinhibitory circuit motif was disclosed, in which VIP neurons inhibit somatostatin (SST) expressing neurons, which in consequence relieves their inhibition from pyramidal cells’ dendritic arbors. However, there is also ample evidence of VIP neurons directly participating in sensory information processing, possibly by mediating feedforward inhibition. How these functions relate to putative specific subtypes of VIP neurons remains to be shown since it was so far not possible to identify these, if there are any. Recently, a novel intersectional approach of studying genetically defined neurons has been published, which led to the making of Cre- and Flp-dependent driver lines that showed as VIP/Calretinin and VIP/Cholecystokinin cells only little overlapping distributions, and were suggested to represent interneuron-specific interneurons and small basket cells, respectively. Here, we will multimodally characterize these (and other) cells and test, via paired and triple recordings, if their connectivity motifs are in agreement with this hypothesis. Furthermore, with patch-seq we will provide a thorough molecular characterization of the VIP neurons. This study has the potential to substantially improve our knowledge on VIP neuron diversity and their putative involvement in sensory information processing.

通过CRE驱动系获得的基因使表达血管活性肠多肽(VIP)的神经元成为重大发现的主题，例如，它们在学习环境中发出奖惩的全脑信号。还揭示了一个丰富的去抑制回路基序，其中VIP神经元抑制生长抑素(SST)表达的神经元，从而解除它们对锥体细胞树突的抑制。然而，也有充分的证据表明，VIP神经元直接参与了感觉信息处理，可能是通过介导前馈抑制。这些功能如何与假定的VIP神经元的特定亚型有关仍有待研究，因为到目前为止，如果有的话，还不可能识别这些亚型。最近，一种新的研究遗传定义神经元的交叉方法被发表，这导致了Cre和FLP依赖的驱动系的建立，这些驱动系显示VIP/Calretinin和VIP/Cholecystokinin细胞仅有很少的重叠分布，并被建议分别代表神经元间特异性中间神经元和小篮子细胞。在这里，我们将对这些(和其他)细胞进行多模式表征，并通过配对和三重录音来测试它们的连接主题是否符合这一假设。此外，通过PATCH-SEQ，我们将提供VIP神经元的完整分子特征。这项研究有可能极大地提高我们对VIP神经元多样性及其参与感觉信息处理的知识。