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

通过cre驱动系的遗传通路使得表达血管活性肠多肽（VIP）的神经元成为重大发现的主题，例如它们在学习背景下的奖励或惩罚的全脑信号。此外，还发现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，从而减轻了它们对锥体细胞树突乔木的抑制。然而，也有充分的证据表明VIP神经元直接参与感觉信息加工，可能是通过介导前馈抑制。这些功能如何与假定的VIP神经元的特定亚型相关仍有待证明，因为迄今为止还不可能识别这些亚型，如果有的话。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依赖性驱动系的产生，这些驱动系显示VIP/Calretinin和VIP/Cholecystokinin细胞只有很少的重叠分布，并被认为分别代表神经元特异性的中间神经元和小篮子细胞。在这里，我们将多模态地表征这些（和其他）细胞，并通过配对和三重记录来测试它们的连接基序是否与这一假设一致。此外，通过patch-seq，我们将提供VIP神经元的全面分子表征。这项研究有可能大大提高我们对VIP神经元多样性及其在感觉信息处理中的假设参与的认识。

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.