Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Present address: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
J Comp Neurol. 2023 Jan;531(1):5-24. doi: 10.1002/cne.25405. Epub 2022 Oct 10.
In the spinal cord, sensory-motor circuits controlling motor activity are situated in the dorso-ventral interface. The neurons identified by the expression of the transcription factor Doublesex and mab-3 related transcription factor 3 (Dmrt3) have previously been associated with the coordination of locomotion in horses (Equus caballus, Linnaeus, 1758), mice (Mus musculus, Linnaeus, 1758), and zebrafish (Danio rerio, F. Hamilton, 1822). Based on earlier studies, we hypothesized that, in mice, these neurons may be positioned to receive sensory and central inputs to relay processed commands to motor neurons. Thus, we investigated the presynaptic inputs to spinal Dmrt3 neurons using monosynaptic retrograde replication-deficient rabies tracing. The analysis showed that lumbar Dmrt3 neurons receive inputs from intrasegmental neurons, and intersegmental neurons from the cervical, thoracic, and sacral segments. Some of these neurons belong to the excitatory V2a interneurons and to plausible Renshaw cells, defined by the expression of Chx10 and calbindin, respectively. We also found that proprioceptive primary sensory neurons of type Ia2, Ia3, and Ib, defined by the expression of calbindin, calretinin, and Brn3c, respectively, provide presynaptic inputs to spinal Dmrt3 neurons. In addition, we demonstrated that Dmrt3 neurons receive inputs from brain areas involved in motor regulation, including the red nucleus, primary sensory-motor cortex, and pontine nuclei. In conclusion, adult spinal Dmrt3 neurons receive inputs from motor-related brain areas as well as proprioceptive primary sensory neurons and have been shown to connect directly to motor neurons. Dmrt3 neurons are thus positioned to provide sensory-motor control and their connectivity is suggestive of the classical reflex pathways present in the spinal cord.
在脊髓中，控制运动活动的感觉运动回路位于背腹界面。先前已经发现，表达转录因子双性和 mab-3 相关转录因子 3（Dmrt3）的神经元与马（Equus caballus，Linnaeus，1758）、小鼠（Mus musculus，Linnaeus，1758）和斑马鱼（Danio rerio，F. Hamilton，1822）的运动协调有关。基于早期的研究，我们假设在小鼠中，这些神经元可能位于接收感觉和中枢输入的位置，以将处理后的命令传递给运动神经元。因此，我们使用单突触逆行复制缺陷型狂犬病毒追踪法研究了脊髓 Dmrt3 神经元的突触前输入。分析表明，腰段 Dmrt3 神经元接收来自节内神经元的输入，来自颈段、胸段和骶段的神经元接收来自节间神经元的输入。其中一些神经元属于兴奋性 V2a 中间神经元和可能的 Renshaw 细胞，分别由 Chx10 和 calbindin 的表达定义。我们还发现，分别由 calbindin、calretinin 和 Brn3c 表达定义的 Ia2、Ia3 和 Ib 型本体感觉初级感觉神经元为脊髓 Dmrt3 神经元提供突触前输入。此外，我们证明 Dmrt3 神经元接收来自参与运动调节的脑区的输入，包括红核、初级感觉运动皮层和脑桥核。总之，成年脊髓 Dmrt3 神经元接收来自运动相关脑区以及本体感觉初级感觉神经元的输入，并已被证明直接连接到运动神经元。因此，Dmrt3 神经元能够提供感觉运动控制，其连接性表明脊髓中存在经典的反射通路。
