小柯机器人

研究揭示区域间皮层投射神经元命运多样性的时间控制
2021-11-13 14:10

瑞士日内瓦大学Denis Jabaudon团队揭示区域间皮层投射神经元命运多样性的时间控制。相关论文于2021年11月9日在线发表在《自然》杂志上。

研究人员表示,新皮质区域之间的互连对于感觉统合和感觉运动转换至关重要。这些功能由异质区域间皮层投射神经元(ICPN)介导,ICPN将轴突分支发送到皮层区域以及皮层下靶标。尽管ICPN在解剖结构上多种多样,但它们在分子上是同质的,并且在发育过程中它们的解剖和功能特征的多样性如何出现在很大程度上仍然未知。

研究人员通过结合测序(MAPseq,用于鉴别单神经元轴突投影)和单细胞RNA测序(用于确定相应的基因表达)来解决了这个问题。通过关注于初级体感皮层(S1)的神经元,研究人员揭示了运动皮层投射(M→)ICPN与次级体感皮层投射(S2→)ICPN 相比,分子和功能分化的持续展开。研究人员将SOX11鉴定为M→与S2→ICPN中时间差异表达的转录因子。出生后对S1中SOX11表达的操纵损害了小鼠的感觉运动连接并破坏了选择性探索行为。

总之,这些结果表明,在单个皮质区域内,不同亚型的ICPN具有不同的出生后分子分化速度,随后反映在不同的回路连接和功能中。因此,大量通用基因表达水平的动态差异,而不是发育遗传程序身份的根本差异,可能是皮质神经元类型内多样性出现的原因。

附:英文原文

Title: Temporal controls over inter-areal cortical projection neuron fate diversity

Author: Klingler, Esther, Tomasello, Ugo, Prados, Julien, Kebschull, Justus M., Contestabile, Alessandro, Galianes, Gregorio L., Fivre, Sabine, Santinha, Antonio, Platt, Randal, Huber, Daniel, Dayer, Alexandre, Bellone, Camilla, Jabaudon, Denis

Issue&Volume: 2021-11-09

Abstract: Interconnectivity between neocortical areas is critical for sensory integration and sensorimotor transformations1,2,3,4,5,6. These functions are mediated by heterogeneous inter-areal cortical projection neurons (ICPN), which send axon branches across cortical areas as well as to subcortical targets7,8,9. Although ICPN are anatomically diverse10,11,12,13,14, they are molecularly homogeneous15, and how the diversity of their anatomical and functional features emerge during development remains largely unknown. Here we address this question by linking the connectome and transcriptome in developing single ICPN of the mouse neocortex using a combination of multiplexed analysis of projections by sequencing16,17 (MAPseq, to identify single-neuron axonal projections) and single-cell RNA sequencing (to identify corresponding gene expression). Focusing on neurons of the primary somatosensory cortex (S1), we reveal a protracted unfolding of the molecular and functional differentiation of motor cortex-projecting (M ) ICPN compared with secondary somatosensory cortex-projecting (S2→) ICPN. We identify SOX11 as a temporally differentially expressed transcription factor in M  versus S2→ ICPN. Postnatal manipulation of SOX11 expression in S1 impaired sensorimotor connectivity and disrupted selective exploratory behaviours in mice. Together, our results reveal that within a single cortical area, different subtypes of ICPN have distinct postnatal paces of molecular differentiation, which are subsequently reflected in distinct circuit connectivities and functions. Dynamic differences in the expression levels of a largely generic set of genes, rather than fundamental differences in the identity of developmental genetic programs, may thus account for the emergence of intra-type diversity in cortical neurons.

DOI: 10.1038/s41586-021-04048-3

Source: https://www.nature.com/articles/s41586-021-04048-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

分享到:

0