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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Posted ContentDOI
Evaluation of calcium-sensitive adenylyl cyclase AC1 and AC8 mRNA expression in the anterior cingulate cortex of mice with neuropathic pain
TL;DR: In this paper, the authors conducted RNAscope in situ hybridization to assess AC1 and AC8 mRNA distribution in mice with spared nerve injury (SNI), and they found that SNI causes an increase in AC 8 mRNA expression in NMDAR-2B (Nr2b) positive neurons in the contralateral ACC but does not affect AC1 mRNA expression.
References
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Book
The Mouse Brain in Stereotaxic Coordinates
TL;DR: The 3rd edition of this atlas is now in more practical 14"x11" format for convenient lab use and includes a CD of all plates and diagrams, as well as Adobe Illustrator files of the diagrams, and a variety of additional useful material.
Journal ArticleDOI
Representation of Pain and Somatic Sensation in the Human Insula: a Study of Responses to Direct Electrical Cortical Stimulation
TL;DR: It is found that painful and non-painful somaesthetic representations in the human insula overlap, and lateralization in the right hemisphere of sites where painful sensations were evoked is coherent with the hypothesis of a preponderant role of this hemisphere in species survival.
Journal ArticleDOI
Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice.
Austen J. Milnerwood,Clare M. Gladding,Mahmoud A. Pouladi,Alexandra M. Kaufman,Rochelle M. Hines,Jamie D. Boyd,Rebecca W.Y. Ko,Oana Cristina Vasuta,Rona K. Graham,Michael R. Hayden,Timothy H. Murphy,Lynn A. Raymond +11 more
TL;DR: Elevated extrasynaptic NMDAR activity is demonstrated in an animal model of neurodegenerative disease and a candidate mechanism linking several pathways previously implicated in HD pathogenesis is provided and successful early therapeutic intervention in mice is demonstrated.
Journal ArticleDOI
Roles of NMDA NR2B Subtype Receptor in Prefrontal Long-Term Potentiation and Contextual Fear Memory
Ming Gao Zhao,Hiroki Toyoda,Yong-Seok Lee,Yong-Seok Lee,Long Jun Wu,Long Jun Wu,Shanelle W. Ko,Xue Han Zhang,Yongheng Jia,Fanny W.F. Shum,Hui Xu,Bao Ming Li,Bong-Kiun Kaang,Bong-Kiun Kaang,Min Zhuo,Min Zhuo +15 more
TL;DR: It is reported that the activation of the NR2B and NR2A subunits of the NMDA receptor is critical for the induction of cingulate LTP, regardless of the induction protocol.
Journal ArticleDOI
Calcium-Permeable AMPA Receptor Dynamics Mediate Fear Memory Erasure
Roger L. Clem,Richard L. Huganir +1 more
TL;DR: It is found that a central component of extinction-induced erasure is the synaptic removal of calcium-permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) in the lateral amygdala, which defines a temporal window in which fear memory can be degraded by behavioral experience.
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