Changes in thalamic extrasynaptic GABA-A receptor-mediated currents following peripheral nerve injury and its influence on the remodeling of thalamic afferent fibers

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19195
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pain science
• Research Institution: University of Tsukuba
• Principal Investigator: NAGUMO Yasuyuki 筑波大学, 国際統合睡眠医科学研究機構, 助教 (00459661)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 脳・神経 / 体性感覚視床 / 末梢神経損傷 / GABA シナプス / 内側毛帯線維 / 神経回路再改編 / 痛覚過敏反応

Outline of Final Research Achievements

Peripheral nerve injury induces functional and structural remodeling of neural circuits along the somatosensory pathway, and this remodeling is thought to underlie ectopic abnormal sensation. However, molecular mechanism of injury-induced remodeling is largely unknown. We have previously reported the transection of the infraorbital nerve remodels excitatory lemniscal fiber synapses to somatosensory thalamic neurons. Here we found that extrasynaptic GABA-A receptor (GABA-A R)-mediated currents in the thalamic neuron were potentiated soon after the transection before the remodeling. Pharmacological potentiation of thalamic extrasynaptic GABA-A R currents in intact mice induced the similar abnormal remodeling. Notably, conditional knockout of extrasynaptic GABA-A Rs in the thalamus rescued the injury-induced remodeling as well as the ectopic mechanical hypersensitivity. Together, our results uncover a molecular basis of neural remodeling in the thalamus after peripheral nerve injury.

Free Research Field

神経生理、神経薬理