Department of Basic Neurosciences, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.
1] Department of Basic Neurosciences, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland [2] Interdisciplinary Institute for NeuroScience, CNRS UMR 5297, 33077 Bordeaux, France.
Nature. 2014 Jul 24;511(7510):471-4. doi: 10.1038/nature13390. Epub 2014 May 14.
During development, thalamocortical (TC) input has a critical role in the spatial delineation and patterning of cortical areas, yet the underlying cellular and molecular mechanisms that drive cortical neuron differentiation are poorly understood. In the primary (S1) and secondary (S2) somatosensory cortex, layer 4 (L4) neurons receive mutually exclusive input originating from two thalamic nuclei: the ventrobasalis (VB), which conveys tactile input, and the posterior nucleus (Po), which conveys modulatory and nociceptive input. Recently, we have shown that L4 neuron identity is not fully committed postnatally, implying a capacity for TC input to influence differentiation during cortical circuit assembly. Here we investigate whether the cell-type-specific molecular and functional identity of L4 neurons is instructed by the origin of their TC input. Genetic ablation of the VB at birth resulted in an anatomical and functional rewiring of Po projections onto L4 neurons in S1. This induced acquisition of Po input led to a respecification of postsynaptic L4 neurons, which developed functional molecular features of Po-target neurons while repressing VB-target traits. Respecified L4 neurons were able to respond both to touch and to noxious stimuli, in sharp contrast to the normal segregation of these sensory modalities in distinct cortical circuits. These findings reveal a behaviourally relevant TC-input-type-specific control over the molecular and functional differentiation of postsynaptic L4 neurons and cognate intracortical circuits, which instructs the development of modality-specific neuronal and circuit properties during corticogenesis.
在发育过程中，丘脑皮质（TC）输入在皮质区域的空间划分和模式形成中起着关键作用，但驱动皮质神经元分化的潜在细胞和分子机制仍知之甚少。在初级（S1）和次级（S2）体感皮层中，第 4 层（L4）神经元接收来自两个丘脑核的互斥输入：腹侧基底核（VB），传递触觉输入，以及后核（Po），传递调制和伤害性输入。最近，我们已经表明，L4 神经元的身份在出生后并没有完全确定，这意味着 TC 输入有能力在皮质回路组装过程中影响分化。在这里，我们研究 L4 神经元的细胞类型特异性分子和功能特性是否由其 TC 输入的起源来指导。出生时 VB 的基因消融导致 S1 中 Po 投射到 L4 神经元的解剖和功能重新布线。这种 Po 输入的诱导获得导致 L4 神经元的重新指定，其获得了 Po 靶神经元的功能分子特征，同时抑制了 VB 靶特征。重新指定的 L4 神经元能够对触觉和伤害性刺激做出反应，与这些感觉模态在不同皮质回路中的正常分离形成鲜明对比。这些发现揭示了一种行为相关的 TC 输入类型特异性控制，对突触后 L4 神经元和同源皮质内回路的分子和功能分化进行了控制，从而指导了皮质发生过程中特定模态的神经元和回路特性的发育。
