Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Mol Pain. 2014 Jun 3;10:33. doi: 10.1186/1744-8069-10-33.
Long-term potentiation (LTP) is the key cellular mechanism for physiological learning and pathological chronic pain. In the anterior cingulate cortex (ACC), postsynaptic recruitment or modification of AMPA receptor (AMPAR) GluA1 contribute to the expression of LTP. Here we report that pyramidal cells in the deep layers of the ACC send direct descending projecting terminals to the dorsal horn of the spinal cord (lamina I-III). After peripheral nerve injury, these projection cells are activated, and postsynaptic excitatory responses of these descending projecting neurons were significantly enhanced. Newly recruited AMPARs contribute to the potentiated synaptic transmission of cingulate neurons. PKA-dependent phosphorylation of GluA1 is important, since enhanced synaptic transmission was abolished in GluA1 phosphorylation site serine-845 mutant mice. Our findings provide strong evidence that peripheral nerve injury induce long-term enhancement of cortical-spinal projecting cells in the ACC. Direct top-down projection system provides rapid and profound modulation of spinal sensory transmission, including painful information. Inhibiting cortical top-down descending facilitation may serve as a novel target for treating neuropathic pain.
长时程增强（LTP）是生理学习和病理性慢性疼痛的关键细胞机制。在前扣带皮层（ACC）中，AMPA 受体（AMPAR）GluA1 的突触后募集或修饰有助于 LTP 的表达。在这里，我们报告说，ACC 深层的锥体神经元向脊髓背角（I-III 层）发送直接的下行投射末端。在外周神经损伤后，这些投射细胞被激活，并且这些下行投射神经元的突触后兴奋性反应显著增强。新募集的 AMPAR 有助于增强扣带神经元的突触传递。PKA 依赖性 GluA1 磷酸化很重要，因为在 GluA1 磷酸化位点丝氨酸-845 突变小鼠中，增强的突触传递被消除。我们的发现提供了强有力的证据，证明外周神经损伤诱导 ACC 中皮质脊髓投射细胞的长期增强。直接自上而下的投射系统为脊髓感觉传递（包括疼痛信息）提供了快速而深刻的调制。抑制皮质自上而下的促进作用可能成为治疗神经性疼痛的新靶点。
