Institute for Physiology, Faculty of Medicine, University of Freiburg, 79108 Freiburg, Germany; BrainLinks-BrainTools, IMBIT (Institute for Machine-Brain Interfacing Technology), University of Freiburg, Georges-Köhler-Allee 201, 79110 Freiburg, Germany.
Institute for Physiology, Faculty of Medicine, University of Freiburg, 79108 Freiburg, Germany.
Cell Rep. 2024 May 28;43(5):114212. doi: 10.1016/j.celrep.2024.114212. Epub 2024 May 13.
Diverse types of inhibitory interneurons (INs) impart computational power and flexibility to neocortical circuits. Whereas markers for different IN types in cortical layers 2-6 (L2-L6) have been instrumental for generating a wealth of functional insights, only the recent identification of a selective marker (neuron-derived neurotrophic factor [NDNF]) has opened comparable opportunities for INs in L1 (L1INs). However, at present we know very little about the connectivity of NDNF L1INs with other IN types, their input-output conversion, and the existence of potential NDNF L1IN subtypes. Here, we report pervasive inhibition of L2/3 INs (including parvalbumin INs and vasoactive intestinal peptide INs) by NDNF L1INs. Intersectional genetics revealed similar physiology and connectivity in the NDNF L1IN subpopulation co-expressing neuropeptide Y. Finally, NDNF L1INs prominently and selectively engage in persistent firing, a physiological hallmark disconnecting their output from the current input. Collectively, our work therefore identifies NDNF L1INs as specialized master regulators of superficial neocortex according to their pervasive top-down afferents.
不同类型的抑制性中间神经元 (INs) 为新皮层回路赋予了计算能力和灵活性。虽然皮层层 2-6（L2-L6）中不同 IN 类型的标志物对于产生大量功能见解非常重要，但只有最近才确定了一个选择性标志物（神经元衍生的神经营养因子 [NDNF]），这为 L1（L1INs）中的 INs 提供了类似的机会。然而，目前我们对 NDNF L1INs 与其他 IN 类型的连接、它们的输入-输出转换以及潜在的 NDNF L1IN 亚型的存在知之甚少。在这里，我们报告了 NDNF L1INs 对 L2/3 INs（包括 parvalbumin INs 和血管活性肠肽 INs）的普遍抑制作用。交差遗传揭示了在共表达神经肽 Y 的 NDNF L1IN 亚群中具有相似的生理学和连接性。最后，NDNF L1INs 突出地选择性地进行持续放电，这是一种生理特征，将它们的输出与当前输入断开。总的来说，我们的工作因此根据其广泛的自上而下的传入，将 NDNF L1INs 确定为浅层新皮层的专门主调节因子。
