Connectivity and function of inhibitory neurons in the primate visual cortex

项目总结 在哺乳动物的新皮质中，抑制性神经元(INS)深刻地影响着皮质的计算和 动力学，它们的不同功能被认为是由不同的IN类型介导的。虽然物种的多样性很大 在存在INS的情况下，小鼠皮质中的分子标记识别出三个主要的非重叠类别：小白蛋白- (PV)、生长抑素(SOM)和血管活性肠肽(VIP)INS。小鼠品系中表达基因的研究 这些IN类中的每个类中的Cre重组酶正在迅速揭示出不同的连接、响应模式 每一类的性质和体内功能。然而，目前尚不清楚从以下方面获得的见解 小鼠皮质适用于灵长类动物和人类的皮质胰岛素。在人类功能障碍中被牵连到 几种障碍，如癫痫、精神分裂症、焦虑和自闭症，因此了解 灵长类动物正常的大脑皮层IN连接和功能。缺乏病毒工具来选择性地访问 亚型，以及在灵长类动物中进行遗传操作的困难一直是阻碍 在这个动物模型中研究INS。我们的目标是利用病毒工具开发的最新进展来 在特定的INS亚型中表达转基因以研究连接性、响应特性和 灵长类动物表层两大类INS的计算功能 初级视皮层(V1)。利用Cre重组酶与狂犬病病毒结合的IN型特异性表达 单突触电路跟踪，我们将局部和全脑输入映射到特定的V1 IN类(Aim1)。vbl.使用 IN型特异性靶向钙指示剂的双光子成像，或光遗传学鉴定 通道视紫红质标记的类型，我们将在类中表征不同V1的视觉反应特性 (AIM2)。最后，我们将使用表达抑制性视蛋白的不同IN类型的光遗传失活，以 了解IN类在V1计算中的相对角色(Aim3)。我们将检验推导出的特定假设 根据小鼠的现有数据，发表了灵长类皮质中PV和SOM细胞的特定几何形状 视觉皮层特征调谐和环绕抑制的计算模型，以及我们的初步研究 结果。冲击力。拟议的研究将提供关于连通性、视觉特性和 PV和SOM INS在灵长类皮质中的计算功能，为研究IN在灵长类皮质中的功能奠定了基础 秩序。它们还将揭示跨物种IN功能的保守原则以及基本的 物种差异，强调研究进化物种的皮质功能的重要性 更接近人类。

PROJECT SUMMARY In the mammalian neocortex, inhibitory neurons (INs) profoundly influence cortical computations and dynamics, and their various functions are thought to be mediated by different IN types. While a large diversity of INs exists, molecular markers in mouse cortex identify three major non-overlapping classes: parvalbumin- (PV), somatostatin- (SOM), and vasoactive intestinal peptide- (VIP) INs. Studies in mouse lines expressing Cre-recombinase in each of these IN classes are rapidly revealing distinct patterns of connectivity, response properties and in vivo function for each class. However, it remains unknown whether insights gained from mouse cortex apply to cortical INs in primates and humans. IN dysfunction in humans has been implicated in several disorders, such as epilepsy, schizophrenia, anxiety and autism, therefore it is important to understand normal cortical IN connectivity and function in primates. The lack of viral tools to selectively access IN subtypes, and the difficulty of performing genetic manipulations in primates have been major impediments to studying INs in this animal model. Our goal is to leverage recent advances in the development of viral tools to express transgenes in specific INs subtypes to investigate the connectivity, response properties, and computational function of two major classes of INs, PV and SOM, in the superficial layers of the primate primary visual cortex (V1). Using IN-type specific expression of Cre-recombinase combined with rabies-virus monosynaptic circuit tracing, we will map local and brain-wide inputs to specific V1 IN classes (Aim1). Using two-photon imaging of IN-type specific targeted calcium indicators, or optogenetic identification of channelrhodopsin-tagged IN types, we will characterize the visual response properties of distinct V1 IN classes (Aim2). Finally, we will use optogenetic inactivation of distinct IN-types expressing inhibitory opsins, to understand the relative roles of IN classes in V1 computations (Aim3). We will test specific hypotheses derived from available data in mouse, the specific geometry of PV and SOM cells in primate cortex, published computational models of feature tuning and surround suppression in visual cortex, and our preliminary results. Impact. The proposed studies will provide the first account of the connectivity, visual properties and computational function of PV and SOM INs in primate cortex, paving the way for studies of IN function in this order. They will also reveal conserved principles of IN function across species, as well as fundamental inter- species differences, stressing the importance of studying cortical function in species that are evolutionarily closer to humans.