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Early cortical GABAergic interneurons determine the projection patterns of L4 excitatory neurons

机译:早期皮质 GABA 能中间神经元决定了 L4 兴奋性神经元的投射模式

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摘要

During cerebral cortex development, excitatory pyramidal neurons (PNs) establish specific projection patterns while receiving inputs from GABAergic inhibitory interneurons (INs). Whether these inhibitory inputs can shape PNs’ projection patterns is, however, unknown. While layer 4 (L4) PNs of the primary somatosensory (S1) cortex are all born as long-range callosal projection neurons (CPNs), most of them acquire local connectivity upon activity-dependent elimination of their interhemispheric axons during postnatal development. Here, we demonstrate that precise developmental regulation of inhibition is key for the retraction of S1L4 PNs’ callosal projections. Ablation of somatostatin INs leads to premature inhibition from parvalbumin INs onto S1L4 PNs and prevents them from acquiring their barrel-restricted local connectivity pattern. As a result, adult S1L4 PNs retain interhemispheric projections responding to tactile stimuli, and the mice lose whisker-based texture discrimination. Overall, we show that temporally ordered IN activity during development is key to shaping local ipsilateral S1L4 PNs’ projection pattern, which is required for fine somatosensory processing.
机译:在大脑皮层发育过程中,兴奋性锥体神经元 (PN) 在接收来自 GABA 能抑制性中间神经元 (IN) 的输入时建立特定的投射模式。然而,这些抑制性输入是否可以塑造 PN 的投射模式尚不清楚。虽然初级体感 (S4) 皮层的第 4 层 (L4) PN 都是作为长距离胼胝体投射神经元 (CPN) 出生的,但它们中的大多数在出生后发育过程中其半球间轴突的活动依赖性消除后获得局部连接。在这里,我们证明了抑制的精确发育调节是 S1L4 PN 胼胝体投射回缩的关键。生长抑素 IN 的消融导致小白蛋白 IN 对 S1L4 PN 的过早抑制,并阻止它们获得桶限制性局部连接模式。结果,成年 S1L4 PN 保留了对触觉刺激的半球间突起,小鼠失去了基于胡须的纹理辨别力。总体而言,我们表明发育过程中时间有序的 IN 活动是塑造局部同侧 S1L4 PN 投射模式的关键,这是精细体感处理所必需的。

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