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皮质SST和PV中间神经元在视网膜丘脑精细化自上而下调节中的相互作用。

Reciprocal interaction between cortical SST and PV interneurons in top-down regulation of retinothalamic refinement.

作者信息

Jiang Qiufen, Wu Sherry Jingjing, Fishell Gord, Chen Chinfei

机构信息

Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.

Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.

出版信息

Proc Natl Acad Sci U S A. 2025 Jun 24;122(25):e2504224122. doi: 10.1073/pnas.2504224122. Epub 2025 Jun 18.

Abstract

Refinement of thalamic circuits is crucial for the proper maturation of sensory circuits. In the visual system, this process is regulated by corticothalamic feedback during the experience-dependent phase of development. Yet the cortical circuits modulating this feedback remain elusive. Here, we demonstrate opposing roles for cortical somatostatin (SST) and parvalbumin (PV) interneurons in shaping retinogeniculate connectivity during the thalamic sensitive period (P20-30). Early in the refinement process, SST interneurons promote the strengthening and pruning of retinal inputs in the thalamus, as evidenced by disrupted synaptic refinement following their ablation. In contrast, PV interneurons, which mature later, act as a brake on this refinement, with their ablation leading to enhanced pruning of retinogeniculate connections. Notably, manipulating the relative balance between these inhibitory circuits can regulate sensory deprivation-induced retinogeniculate remodeling. Taken together, our findings show that cortical SST and PV interneuron circuits drive experience-dependent reciprocal antagonism that gates cortical feedback regulation of feedforward thalamic refinement.

摘要

丘脑回路的精细化对于感觉回路的正常成熟至关重要。在视觉系统中,这一过程在发育的经验依赖阶段受皮质丘脑反馈调节。然而,调节这种反馈的皮质回路仍不清楚。在这里,我们证明了皮质生长抑素(SST)和小白蛋白(PV)中间神经元在丘脑敏感期(P20 - 30)塑造视网膜 - 膝状体连接中具有相反作用。在精细化过程早期,SST中间神经元促进丘脑中视网膜输入的加强和修剪,这在其被切除后突触精细化受到破坏中得到证明。相反,成熟较晚的PV中间神经元对这种精细化起制动作用,其被切除导致视网膜 - 膝状体连接的修剪增强。值得注意的是,操纵这些抑制性回路之间的相对平衡可以调节感觉剥夺诱导的视网膜 - 膝状体重塑。综上所述,我们的研究结果表明,皮质SST和PV中间神经元回路驱动经验依赖的相互拮抗作用,从而控制皮质对丘脑前馈精细化的反馈调节。

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