Inhibitory and disinhibitory VIP IN-mediated circuits in neocortex.

bioRxiv : the preprint server for biology Pub Date : 2025-05-17 DOI:10.1101/2025.02.26.640383

Shlomo Dellal, Hector Zurita, Ilya Kruglikov, Manuel Valero, Pablo Abad-Perez, Erez Geron, John Hongyu Meng, Alvar Pronneke, Jessica L Hanson, Ema Mir, Marina Ongaro, Xiao-Jing Wang, Gyorgy Buzsaki, Robert P Machold, Bernardo Rudy

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Abstract

Cortical GABAergic interneurons (INs) expressing the neuropeptide vasoactive-intestinal peptide (VIP) predominantly function by inhibiting dendritic-targeting somato-statin (SST) expressing INs, thereby disinhibiting pyramidal cells (PCs) and facilitating cortical circuit plasticity. VIP INs are a molecularly heterogeneous group, but the physiological significance of this diversity is unclear at present. Here, we have characterized the functional diversity of VIP INs in the primary somatosensory cortex (vS1) using intersectional genetic approaches. We found that VIP INs are comprised of four primary populations that exhibit different laminar distributions, axonal and dendritic arbors, intrinsic electrophysiological properties, and efferent connectivity. Furthermore, we observe that these populations are differentially activated by long-range inputs, and display distinct responses to neuromodulation by endocannabinoids, acetylcholine and noradrenaline. Stimulation of VIP IN subpopulations in vivo results in differential effects on the cortical network, thus providing evidence for specialized modes of VIP IN-mediated regulation of PC activity during cortical information processing.

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新皮层VIP in介导的抑制和去抑制回路。

皮层GABAergic interneurons （INs）由不同类型的神经元组成，这些神经元对锥体细胞（PCs）和其他INs提供针对性的抑制，从而能够精确控制皮层回路的活动。表达神经肽血管活性肠肽（VIP）的INs最近引起了人们的关注，因为人们发现INs主要通过抑制树突靶向生长抑素（SST）表达INs，从而解除对PCs的抑制。这种VIP-SST去抑制回路基序在小鼠和人类的整个新皮质中都被观察到，并且是自上而下（反馈）和上下文依赖信息处理的关键机制。因此，VIP in介导的去抑制在感觉加工、执行功能控制、注意、感觉运动整合以及其他皮质-皮质和丘脑皮质反馈相互作用中发挥着重要作用。此外，VIP INs通过对乙酰胆碱（ACh）等神经调节剂的反应，参与介导奖励和厌恶强化信号的作用，并促进突触可塑性和学习。虽然从转录组学分析中可以明显看出VIP INs是一个分子异质性群体，但目前尚不清楚这种多样性的生理意义。在这里，我们利用交叉遗传学方法研究不同的VIP in亚型，表征了初级体感觉皮层VIP in的功能多样性。我们发现VIP INs可以分为四个不同的群体：一个表达ca2 +结合蛋白calretinin （CR）的群体，两个不同的表达神经肽胆囊收缩素（CCK）的群体，以及一个既不表达CR也不表达CCK的群体(非CCK非CR；或nCCK nCR)。各组VIP神经元表现出不同的层流分布、轴突和树突分支、固有电生理特性和输出连性，VIP/CR INs几乎完全靶向SST INs， VIP/nCCK nCR INs也主要靶向SST INs，但也与表达小蛋白（PV）的INs有联系。这两组细胞基本上与锥体细胞（PCs）没有联系。另一方面，两种类型的VIP/CCK INs靶向pc，但每种类型的突触释放受内源性大麻素调节的程度不同。我们还发现，远程输入在招募不同的VIP群体方面存在差异。有趣的是，我们发现不同的VIP IN群体反过来靶向不同的SST INs亚型，这表明存在专门的VIP-SST去抑制亚回路。体内不同VIP IN亚群的激活会对皮层网络产生不同的影响，从而为皮层信息处理过程中VIP IN介导的作用的模块化提供了证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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bioRxiv : the preprint server for biology

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