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
Citations
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Synaptic plasticity in the anterior cingulate cortex in acute and chronic pain
TL;DR: Increasing evidence from rodent studies that ACC activation contributes to chronic pain states is discussed and several forms of synaptic plasticity that may underlie this effect are described.
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Role of the Prefrontal Cortex in Pain Processing.
TL;DR: The medial PFC (mPFC) could serve dual, opposing roles in pain: it mediates antinociceptive effects, due to its connections with other cortical areas, and as the main source of cortical afferents to the PAG for modulation of pain.
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Why fish do not feel pain
TL;DR: It is concluded that fish lack the necessary neurocytoarchitecture, microcircuitry, and structural connectivity for the neural processing required for feeling pain.
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Insular Cortex is Critical for the Perception, Modulation, and Chronification of Pain.
TL;DR: This review discusses the latest data proposing that subregions of the IC are involved in isolated pain networks: the posterior sensory circuit and the anterior emotional network.
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Insects have the capacity for subjective experience
Colin Klein,Andrew B. Barron +1 more
TL;DR: It is argued that the insect brain supports functions analogous to those of the vertebrate midbrain and hence that insects may also have a capacity for subjective experience.
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