Deconstruction the feedforward inhibition changes in the layer III of anterior cingulate cortex after peripheral nerve injury

• Published in: Communications biology 2024-10, Vol.7 (1), p.1237-13, Article 1237
• Main Authors: Lian, Yan-Na, Cao, Xiao-Wen, Wu, Cheng, Pei, Chen-Yu, Liu, Li, Zhang, Chen, Li, Xiang-Yao
• Format: Article
• Language: English
• Subjects: 13/1; 13/51; 14/1; 14/34; 14/35; 14/5; 14/63; 38/1; 38/35; 38/5; 59/5; 631/378/1689/2610; 631/378/3920; 64/60; 9/74; Animals; Aversion; Biomedical and Life Sciences; Brain injury; Cortex (cingulate); Gyrus Cinguli - physiopathology; Hypersensitivity; Information processing; Life Sciences; Male; Mice; Mice, Inbred C57BL; Neural Inhibition; Neurons - physiology; Pain; Peripheral Nerve Injuries - physiopathology; Peripheral nerves; Peroneal nerve; Peroneal Nerve - injuries; Peroneal Nerve - physiopathology; Thalamus - physiopathology
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06849-4

The anterior cingulate cortex (ACC) is one of the critical brain areas for processing noxious information. Previous studies showed that peripheral nerve injury induced broad changes in the ACC, contributing to pain hypersensitivity. The neurons in layer 3 (L3) of the ACC receive the inputs from the mediodorsal thalamus (MD) and form the feedforward inhibition (FFI) microcircuits. The effects of peripheral nerve injury on the MD-driven FFI in L3 of ACC are unknown. In our study, we record the enhanced excitatory synaptic transmissions from the MD to L3 of the ACC in mice with common peroneal nerve ligation, affecting FFI. Chemogenetically activating the MD-to-ACC projections induces pain sensitivity and place aversion in naive mice. Furthermore, chemogenetically inactivating MD-to-ACC projections decreases pain sensitivity and promotes place preference in nerve-injured mice. Our results indicate that the peripheral nerve injury changes the MD-to-ACC projections, contributing to pain hypersensitivity and aversion. Injury-induced changes in MD-to-L3 projections, leading to increased feed forward inhibition, contribute to both pain aversion and altered pain thresholds. Manipulating these inputs affects pain-related behaviors, highlighting their role in pathological pain.