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

通过Cre-driver lines的遗传访问使表达血管活性肠多肽（VIP）的神经元成为重大发现的主题，例如在学习的背景下，它们的全脑奖励或惩罚信号。还公开了丰富的去抑制回路基序，其中VIP神经元抑制表达生长抑素（SST）的神经元，这因此解除了它们对锥体细胞的树突状乔木的抑制。然而，也有充分的证据表明VIP神经元直接参与感觉信息处理，可能是通过介导前馈抑制。这些功能如何与VIP神经元的假定特定亚型相关仍有待证明，因为到目前为止还不可能确定这些亚型（如果有的话）。最近，一种新的交叉方法研究遗传定义的神经元已经出版，这导致了Cre和Flp依赖的驱动线，显示为VIP/Calretinin和VIP/Cholestokinin细胞只有很少的重叠分布，并建议分别代表中间神经元特异性的中间神经元和小篮状细胞。在这里，我们将多模态表征这些（和其他）细胞，并通过配对和三重记录测试，如果它们的连接基序与这一假设一致。此外，通过patch-seq，我们将提供VIP神经元的彻底分子表征。这项研究有可能大大提高我们对VIP神经元多样性及其参与感觉信息处理的认识。

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.