Department of Pain Medicine, Department of Anesthesiology & Perioprative Medicine, 66352Xijing Hospital, 12644Fourth Military Medical University, Xi'an, China.
Mol Pain. 2021 Jan-Dec;17:1744806921992620. doi: 10.1177/1744806921992620.
Spinal GABAergic neurons act as a critical modulator in sensory transmission like pain or itch. The monosynaptic or polysynaptic primary afferent inputs onto GABAergic neurons, along with other interneurons or projection neurons make up the direct and feed-forward inhibitory neural circuits. Previous research indicates that spinal GABAergic neurons mainly receive excitatory inputs from Aδ and C fibers. However, whether they are controlled by other inhibitory sending signals is not well understood.
We applied a transgenic mouse line in which neurons co-expressed the GABA-synthesizing enzyme Gad65 and the enhanced red fluorescence (td-Tomato) to characterize the features of morphology and electrophysiology of GABAergic neurons. Patch-clamp whole cell recordings were used to record the evoked postsynaptic potentials of fluorescent neurons in spinal slices in response to dorsal root stimulation.
We demonstrated that GABAergic neurons not only received excitatory drive from peripheral Aβ, Aδ and C fibers, but also received inhibitory inputs driven by Aδ and C fibers. The evoked inhibitory postsynaptic potentials (eIPSPs) mediated by C fibers were mainly Glycinergic (66.7%) as well as GABAergic mixed with Glycinergic (33.3%), whereas the inhibition mediated by Aδ fibers was predominately both GABA and Glycine-dominant (57.1%), and the rest of which was purely Glycine-dominant (42.9%).
These results indicated that spinal GABAergic inhibitory neurons are under feedforward inhibitory control driven by primary C and Aδ fibers, suggesting that this feed-forward inhibitory pathway may play an important role in balancing the excitability of GABAergic neurons in spinal dorsal horn.
脊髓 GABA 能神经元作为一种重要的调节因子，参与痛觉或痒觉等感觉传递。单突触或多突触初级传入纤维投射到 GABA 能神经元，与其他中间神经元或投射神经元一起构成直接的、前馈抑制性神经回路。先前的研究表明，脊髓 GABA 能神经元主要接受 Aδ 和 C 纤维的兴奋性输入。然而，它们是否受到其他抑制性传递信号的控制还不太清楚。
我们应用了一种转基因小鼠品系，其中神经元共表达 GABA 合成酶 Gad65 和增强型红色荧光蛋白（td-Tomato），以描述 GABA 能神经元的形态和电生理特征。在脊髓切片中，我们应用膜片钳全细胞记录的方法，记录背根刺激后荧光神经元的诱发突触后电位。
我们证明 GABA 能神经元不仅接受外周 Aβ、Aδ 和 C 纤维的兴奋性驱动，还接受 Aδ 和 C 纤维驱动的抑制性输入。C 纤维介导的诱发抑制性突触后电位（eIPSPs）主要是甘氨酸能（66.7%），也有 GABA 能与甘氨酸能混合（33.3%），而 Aδ 纤维介导的抑制主要是 GABA 和甘氨酸能混合（57.1%），其余的是单纯甘氨酸能（42.9%）。
这些结果表明，脊髓 GABA 能抑制性神经元受到初级 C 和 Aδ 纤维的前馈抑制性控制，提示这种前馈抑制性通路可能在平衡脊髓背角 GABA 能神经元的兴奋性方面发挥重要作用。
