Research Unit in Neural Circuit Development, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC, Canada.
Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada.
Pain. 2021 Jan;162(1):161-175. doi: 10.1097/j.pain.0000000000002012.
Anterolateral system (AS) neurons relay nociceptive information from the spinal cord to the brain, protecting the body from harm by evoking a variety of behaviours and autonomic responses. The developmental programs that guide the connectivity of AS neurons remain poorly understood. Spinofugal axons cross the spinal midline in response to Netrin-1 signalling through its receptor deleted in colorectal carcinoma (DCC); however, the relevance of this canonical pathway to AS neuron development has only been demonstrated recently. Here, we disrupted Netrin-1:DCC signalling developmentally in AS neurons and assessed the consequences on the path finding of the different classes of spinofugal neurons. Many lamina I AS neurons normally innervate the lateral parabrachial nucleus and periaqueductal gray on the contralateral side. The loss of DCC in the developing spinal cord resulted in increased frequency of ipsilateral projection of spinoparabrachial and spinoperiaqueductal gray neurons. Given that contralateral spinofugal projections are largely associated with somatotopic representation of the body, changes in the laterality of AS spinofugal projections may contribute to reduced precision in pain localization observed in mice and humans carrying Dcc mutations.
前外侧系统 (AS) 神经元将来自脊髓的伤害性信息传递到大脑，通过引发各种行为和自主反应来保护身体免受伤害。指导 AS 神经元连接的发育程序仍知之甚少。脊髓腹侧的轴突在 Netrin-1 信号的作用下穿过脊髓中线，该信号通过其受体结肠癌缺失 (DCC) 进行传递；然而，最近才证明了这个经典途径对 AS 神经元发育的相关性。在这里，我们在 AS 神经元中发育性地破坏了 Netrin-1:DCC 信号，并评估了对不同类型的脊髓腹侧神经元的路径发现的影响。许多通常支配对侧外侧臂旁核和导水管周围灰质的 I 层 AS 神经元。发育中的脊髓中 DCC 的缺失导致 spinoparabrachial 和 spinoperiaqueductal gray 神经元同侧投射的频率增加。鉴于对侧脊髓腹侧投射主要与身体的躯体定位有关，AS 脊髓腹侧投射的偏侧性变化可能导致携带 Dcc 突变的小鼠和人类疼痛定位精度降低。
