Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
Department of Neurosurgery, Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands.
Nat Commun. 2016 Sep 8;7:12826. doi: 10.1038/ncomms12826.
Individual cortical layers have distinct roles in information processing. All layers receive cholinergic inputs from the basal forebrain (BF), which is crucial for cognition. Acetylcholinergic receptors are differentially distributed across cortical layers, and recent evidence suggests that different populations of BF cholinergic neurons may target specific prefrontal cortical (PFC) layers, raising the question of whether cholinergic control of the PFC is layer dependent. Here we address this issue and reveal dendritic mechanisms by which endogenous cholinergic modulation of synaptic plasticity is opposite in superficial and deep layers of both mouse and human neocortex. Our results show that in different cortical layers, spike timing-dependent plasticity is oppositely regulated by the activation of nicotinic acetylcholine receptors (nAChRs) either located on dendrites of principal neurons or on GABAergic interneurons. Thus, layer-specific nAChR expression allows functional layer-specific control of cortical processing and plasticity by the BF cholinergic system, which is evolutionarily conserved from mice to humans.
个体皮质层在信息处理中具有不同的作用。所有的皮质层都接收基底前脑（BF）的胆碱能输入，这对于认知至关重要。乙酰胆碱能受体在皮质层中呈差异分布，最近的证据表明，BF 胆碱能神经元的不同群体可能针对特定的前额叶皮质（PFC）层，这就提出了一个问题，即 PFC 的胆碱能控制是否依赖于皮质层。在这里，我们解决了这个问题，并揭示了内源性胆碱能调节突触可塑性的树突机制，这种机制在小鼠和人类新皮质的浅层和深层中是相反的。我们的结果表明，在不同的皮质层中，由烟碱型乙酰胆碱受体（nAChR）的激活引起的、依赖于尖峰时间的可塑性受到位于主神经元树突上或 GABA 能中间神经元上的 nAChR 的相反调节。因此，层特异性 nAChR 表达允许 BF 胆碱能系统对皮质处理和可塑性进行功能上的层特异性控制，这种控制在从老鼠到人类的进化过程中是保守的。
