Sgourdou Paraskevi, Schaffler Melanie, Choi Kyuhyun, McCall Nora M, Burdge Justin, Williams Joelle, Corder Gregory, Fuccillo Marc V, Abdus-Saboor Ishmail, Epstein Douglas J
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Pain. 2025 Jan 1;166(1):130-143. doi: 10.1097/j.pain.0000000000003325. Epub 2024 Aug 23.
The thalamus plays an important role in sensory and motor information processing by mediating communication between the periphery and the cerebral cortex. Alterations in thalamic development have profound consequences on sensory and motor function. In this study, we investigated a mouse model in which thalamic nuclei formation is disrupted because of the absence of Sonic hedgehog ( Shh ) expression from 2 key signaling centers that are required for embryonic forebrain development. The resulting defects observed in distinct thalamic sensory nuclei in Shh mutant embryos persisted into adulthood prompting us to examine their effect on behavioral responses to somatosensory stimulation. Our findings reveal a role for first-order posterior medial thalamic neurons and their projections to layer 4 of the secondary somatosensory cortex in the transmission of nociceptive information. Together, these results establish a connection between a neurodevelopmental lesion in the thalamus and a modality-specific disruption in pain perception.
丘脑通过介导外周与大脑皮层之间的通信,在感觉和运动信息处理中发挥重要作用。丘脑发育的改变对感觉和运动功能有深远影响。在本研究中,我们研究了一种小鼠模型,由于胚胎前脑发育所需的2个关键信号中心缺乏音猬因子(Shh)表达,丘脑核形成受到破坏。在Shh突变胚胎的不同丘脑感觉核中观察到的由此产生的缺陷持续到成年期,促使我们研究它们对体感刺激行为反应的影响。我们的研究结果揭示了一级丘脑后内侧神经元及其向次级体感皮层第4层的投射在伤害性信息传递中的作用。总之,这些结果在丘脑的神经发育损伤与痛觉的模态特异性破坏之间建立了联系。