Postsynaptic Potentiation of Corticospinal Projecting Neurons in the Anterior Cingulate Cortex after Nerve Injury

Tao Chen, Kohei Koga, Giannina Descalzi, Shuang Qiu, Jian Wang, Le-Shi Zhang, Zhi-Jian Zhang, Xiao-Bin He, Xin Qin, Fu-Qiang Xu, Ji Hu, Feng Wei, Richard L Huganir, Yun-Qing Li, Min Zhuo

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.