Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland; Clinic of Neurology, Geneva University Hospital, Geneva, Switzerland.
Curr Biol. 2019 Jan 21;29(2):332-339.e5. doi: 10.1016/j.cub.2018.11.071. Epub 2019 Jan 10.
Neurons of the neocortex are organized into six radial layers, which have appeared at different times during evolution, with the superficial layers representing a more recent acquisition. Input to the neocortex predominantly reaches superficial layers (SL, i.e., layers (L) 2-4), while output is generated in deep layers (DL, i.e., L5-6) [1]. Intracortical connections, which bridge input and output pathways, are key components of cortical circuits because they allow the propagation and processing of information within the neocortex. Two main types of intracortically projecting neurons (ICPN) can be distinguished by their axonal features: L4 spiny stellate neurons (SSN) with short axons projecting locally within cortical columns [2-5], and SL and DL long-range projection neurons, including callosally projecting neurons (CPN and CPN) [5, 6]. Here, we investigate the molecular hallmarks that distinguish SSN, CPN, and CPN and relate their transcriptional signatures with their output connectivity. Specifically, taking advantage of the presence of CPN in both SL and DL, we identify lamina-independent genetic hallmarks of a constant projection motif (i.e., interhemispheric projection). By performing unbiased transcriptomic comparisons between CPN, CPN and SSN, we provide specific molecular profiles for each of these populations and show that target identity supersedes laminar position in defining ICPN transcriptional diversity. Together, these findings reveal a projection-based organization of transcriptional programs across cortical layers, which we propose reflects conserved strategy to protect canonical circuit structure (and hence function) across a diverse range of neuroanatomies.
大脑皮层的神经元组织成 6 个放射状层，这些层在进化过程中出现的时间不同，浅层代表最近的获得。皮质的输入主要到达浅层（SL，即 L2-4 层），而输出则产生于深层（DL，即 L5-6 层）[1]。桥接输入和输出途径的皮质内连接是皮质回路的关键组成部分，因为它们允许信息在新皮层内传播和处理。两种主要类型的皮质内投射神经元（ICPN）可以根据其轴突特征区分：具有短轴突的 L4 棘状星状神经元（SSN）在皮质柱内局部投射[2-5]，以及 SL 和 DL 长程投射神经元，包括胼胝体投射神经元（CPN 和 CPN）[5,6]。在这里，我们研究了区分 SSN、CPN 和 CPN 的分子特征，并将其转录特征与其输出连接相关联。具体来说，利用 CPN 同时存在于 SL 和 DL 中，我们确定了一种恒定投射模式（即半球间投射）的无偏转录特征。通过在 CPN、CPN 和 SSN 之间进行无偏转录组比较，我们为这些群体中的每一个提供了特定的分子特征，并表明靶标身份在定义 ICPN 转录多样性方面取代了层位置。总之，这些发现揭示了跨皮质层的基于投射的转录程序组织，我们提出这反映了在广泛的神经解剖结构中保护经典回路结构（从而保护功能）的保守策略。
