Department of Psychiatry, Columbia University, New York, NY 10032, USA.
Department of Neuroscience, Columbia University, New York, NY 10027, USA; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Neuron. 2019 Mar 20;101(6):1150-1165.e8. doi: 10.1016/j.neuron.2019.01.009. Epub 2019 Jan 31.
Diverse computations in the neocortex are aided by specialized GABAergic interneurons (INs), which selectively target other INs. However, much less is known about how these canonical disinhibitory circuit motifs contribute to network operations supporting spatial navigation and learning in the hippocampus. Using chronic two-photon calcium imaging in mice performing random foraging or goal-oriented learning tasks, we found that vasoactive intestinal polypeptide-expressing (VIP), disinhibitory INs in hippocampal area CA1 form functional subpopulations defined by their modulation by behavioral states and task demands. Optogenetic manipulations of VIP INs and computational modeling further showed that VIP disinhibition is necessary for goal-directed learning and related reorganization of hippocampal pyramidal cell population dynamics. Our results demonstrate that disinhibitory circuits in the hippocampus play an active role in supporting spatial learning. VIDEO ABSTRACT.
大脑皮层中的各种计算过程得益于专门的 GABA 能中间神经元 (IN) 的辅助，这些神经元可以选择性地靶向其他 IN。然而，关于这些经典的抑制性回路基元如何有助于支持空间导航和海马体学习的网络操作，我们知之甚少。在执行随机觅食或目标导向学习任务的小鼠中，我们使用慢性双光子钙成像技术发现，血管活性肠肽表达 (VIP) 的 IN 在海马 CA1 区形成了功能性亚群，其功能由行为状态和任务需求的调节来定义。对 VIP IN 的光遗传学操作和计算模型进一步表明，VIP 抑制对于目标导向学习和海马锥体细胞群体动力学的相关重组是必要的。我们的结果表明，海马中的抑制性回路在支持空间学习方面发挥着积极作用。
