Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University Amsterdam, De Boelelaan 1085, Amsterdam, 1081 HV, The Netherlands.
MRC Centre-Developmental Neurobiology, King's college London, London, WC2R 2LS, UK.
Nat Commun. 2018 Oct 5;9(1):4101. doi: 10.1038/s41467-018-06628-w.
A variety of inhibitory pathways encompassing different interneuron types shape activity of neocortical pyramidal neurons. While basket cells (BCs) mediate fast lateral inhibition between pyramidal neurons, Somatostatin-positive Martinotti cells (MCs) mediate a delayed form of lateral inhibition. Neocortical circuits are under control of acetylcholine, which is crucial for cortical function and cognition. Acetylcholine modulates MC firing, however, precisely how cholinergic inputs affect cortical lateral inhibition is not known. Here, we find that cholinergic inputs selectively augment and speed up lateral inhibition between pyramidal neurons mediated by MCs, but not by BCs. Optogenetically activated cholinergic inputs depolarize MCs through activation of ß2 subunit-containing nicotinic AChRs, not muscarinic AChRs, without affecting glutamatergic inputs to MCs. We find that these mechanisms are conserved in human neocortex. Cholinergic inputs thus enable cortical pyramidal neurons to recruit more MCs, and can thereby dynamically highlight specific circuit motifs, favoring MC-mediated pathways over BC-mediated pathways.
多种抑制性通路包含不同的中间神经元类型，从而塑造了新皮层锥体神经元的活动。篮状细胞 (BCs) 在锥体神经元之间介导快速的侧抑制，而生长抑素阳性的 Martinotti 细胞 (MCs) 则介导延迟形式的侧抑制。新皮层回路受乙酰胆碱的控制，乙酰胆碱对皮质功能和认知至关重要。乙酰胆碱调节 MC 的放电，但胆碱能输入如何影响皮质侧抑制尚不清楚。在这里，我们发现，胆碱能输入选择性地增强和加速了由 MC 介导的而不是由 BC 介导的锥体神经元之间的侧抑制。通过激活含有β2 亚基的烟碱型乙酰胆碱受体，而非毒蕈碱型乙酰胆碱受体，光遗传学激活的胆碱能输入使 MC 去极化，而不影响 MC 上的谷氨酸能输入。我们发现这些机制在人类新皮层中是保守的。因此，胆碱能输入使皮质锥体神经元能够募集更多的 MC，从而可以动态突出特定的回路模式，有利于 MC 介导的通路而不是 BC 介导的通路。
