GluA1 Phosphorylation Contributes to Postsynaptic Amplification of Neuropathic Pain in the Insular Cortex
Shuang Qiu,Ming Zhang,Yan Liu,Yan-yan Guo,Huan Zhao,Qian Song,Ming-gao Zhao,Richard L. Huganir,Jianhong Luo,Hui Xu,Min Zhuo +10 more
TLDR
The results suggest that the expression of AMPARs is enhanced in the insular cortex after nerve injury by a pathway involving AC1, AKAP79/150, and PKA, and such enhancement may at least in part contribute to behavioral sensitization together with other cortical regions, such as the anterior cingulate and the prefrontal cortices.Abstract:
Long-term potentiation of glutamatergic transmission has been observed after physiological learning or pathological injuries in different brain regions, including the spinal cord, hippocampus, amygdala, and cortices. The insular cortex is a key cortical region that plays important roles in aversive learning and neuropathic pain. However, little is known about whether excitatory transmission in the insular cortex undergoes plastic changes after peripheral nerve injury. Here, we found that peripheral nerve ligation triggered the enhancement of AMPA receptor (AMPAR)-mediated excitatory synaptic transmission in the insular cortex. The synaptic GluA1 subunit of AMPAR, but not the GluA2/3 subunit, was increased after nerve ligation. Genetic knock-in mice lacking phosphorylation of the Ser845 site, but not that of the Ser831 site, blocked the enhancement of the synaptic GluA1 subunit, indicating that GluA1 phosphorylation at the Ser845 site by protein kinase A (PKA) was critical for this upregulation after nerve injury. Furthermore, A-kinase anchoring protein 79/150 (AKAP79/150) and PKA were translocated to the synapses after nerve injury. Genetic deletion of adenylyl cyclase subtype 1 (AC1) prevented the translocation of AKAP79/150 and PKA, as well as the upregulation of synaptic GluA1-containing AMPARs. Pharmacological inhibition of calcium-permeable AMPAR function in the insular cortex reduced behavioral sensitization caused by nerve injury. Our results suggest that the expression of AMPARs is enhanced in the insular cortex after nerve injury by a pathway involving AC1, AKAP79/150, and PKA, and such enhancement may at least in part contribute to behavioral sensitization together with other cortical regions, such as the anterior cingulate and the prefrontal cortices.read more
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Nucleus tractus solitarius mediates hyperalgesia induced by chronic pancreatitis in rats.
Yang Bai,Ying-Biao Chen,Xin-Tong Qiu,Yan-Bing Chen,Li-Tian Ma,Ying-Qi Li,Hong-Ke Sun,Mingming Zhang,Ting Zhang,Tao Chen,Bo-Yuan Fan,Hui Li,Yun-Qing Li +12 more
TL;DR: It is suggested that enhanced excitatory transmission within the caudal NTS contributes to pancreatic pain and emphasize the NTS as a pivotal hub for the processing of pancreatic afferents, which provide novel insights into the central sensitization of painful CP.
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Kainate receptor mediated presynaptic LTP in agranular insular cortex contributes to fear and anxiety in mice
Tianyao Shi,Shufang Feng,Mingxiao Wei,Yan Huang,Gang Liu,Haitao Wu,Yong-Xiang Zhang,Wen-Xia Zhou +7 more
TL;DR: The findings suggest that activity‐dependent synaptic plasticity takes place in the AIC due to exposure to fear or anxiety, and inhibiting the presynaptic KAR function may help to prevent or treat anxiety disorder.
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In vivo voltage-sensitive dye imaging of the insular cortex in nerve-injured rats.
TL;DR: The results suggest that the elevated responsiveness of the IC to peripheral stimulation is related to neuropathic pain, and that neuroplastic changes are likely to be involved in the IC after nerve injury.
Journal ArticleDOI
CGRP physiology, pharmacology, and therapeutic targets: Migraine and beyond.
Andrew F. Russo,Debbie L. Hay +1 more
TL;DR: A review of CGRP receptor pharmacology in the peripheral and central nervous systems can be found in this article , which provides a contextual background on the regulation and sites of cG protein-coupled receptors that form unusual complexes with receptor activity modifying proteins.
Journal ArticleDOI
Preferential generation of Ca2+-permeable AMPA receptors by AKAP79-anchored protein kinase C proceeds via GluA1 subunit phosphorylation at Ser-831
TL;DR: It is found that GluA1 phosphorylation at Ser-831 is sufficient for the appearance of CP-AMPARs and that AKAP79-anchored protein kinase C (PKC) primarily drives the appearanceof these receptors via this site, which may reflect the need for these sites to undergo active phosphorylated/dephosphorylation cycles that control their residency within distinct subcellular compartments.
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