Calcium-stimulated adenylyl cyclase subtype 1 is required for presynaptic long-term potentiation in the insular cortex of adult mice

Miao, Huihui; Li, Xu Hui; Chen, Qi-Yu; Zhuo, Min

doi:10.1177/1744806919842961

Cited by 25 publications

(22 citation statements)

References 34 publications

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“…For signaling pathways, the results demonstrated that neuronal AC1 is important for CGRP produced presynaptic enhancement. Previous studies demonstrate that AC1 is cortical for both pre-and post-LTP in the ACC and IC [29,32,38]. These results further support the important roles of AC1 in presynaptic potentiation within cortical synapses.…”

Section: Innervation and Distribution Of Cgrp In The Icsupporting

confidence: 78%

Cortical potentiation induced by calcitonin gene-related peptide (CGRP) in the insular cortex of adult mice

et al. 2020

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Recent studies demonstrate that calcitonin gene-related peptide (CGRP) plays critical roles in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP and its receptors are expressed in cortical areas that are critical for pain perception including the anterior cingulate cortex (ACC) and insular cortex (IC). Recent studies reported that CGRP enhanced excitatory transmission in the ACC. However, little is known about the possible effect of CGRP on excitatory transmission in the IC. In the present study, we investigated the role of CGRP on synaptic transmission in the IC slices of adult male mice. Bath application of CGRP produced dosedependent potentiation of evoked excitatory postsynaptic currents (eEPSCs). This potentiation was NMDA receptor (NMDAR) independent. After application of CGRP1 receptor antagonist CGRP 8-37 or BIBN 4096, CGRP produced potentiation was significantly reduced. Paired-pulse facilitation was significantly decreased by CGRP, suggesting possible presynaptic mechanisms. Consistently, bath application of CGRP significantly increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs). By contrast, amplitudes of sEPSCs and mEPSCs were not significantly affected. Finally, adenylyl cyclase subtype 1 (AC1) and protein kinase A (PKA) are critical for CGRP-produced potentiation, since both selective AC1 inhibitor NB001 and the PKA inhibitor KT5720 completely blocked the potentiation. Our results provide direct evidence that CGRP contributes to synaptic potentiation in the IC, and the AC1 inhibitor NB001 may be beneficial for the treatment of migraine in the future.

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Section: Innervation and Distribution Of Cgrp In The Icsupporting

confidence: 78%

Cortical potentiation induced by calcitonin gene-related peptide (CGRP) in the insular cortex of adult mice

et al. 2020

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show abstract

“…For signaling pathways, we have demonstrated that neuronal AC1 is important for CGRP produced presynaptic enhancement. Previous studies demonstrate that AC1 is cortical for both pre-and post-LTP in the ACC and IC [26,29,34]. These results further support the important roles of AC1 in presynaptic potentiation within cortical synapses.…”

Section: Modulation Of Synaptic Transmission By Cgrp In the Icsupporting

confidence: 78%

Cortical potentiation induced by calcitonin gene-related peptide (CGRP) in the insular cortex of adult mice

Liu

Chen

Lee

et al. 2020

Preprint

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Recent studies demonstrate that calcitonin gene-related peptide (CGRP) plays critical roles in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP and its receptors are expressed in cortical areas that are critical for pain perception including the anterior cingulate cortex (ACC) and insular cortex (IC). Recent studies reported that CGRP enhanced excitatory transmission in the ACC. However, little is known about the possible effect of CGRP on excitatory transmission in the IC. In the present study, we investigated the role of CGRP on synaptic transmission in the IC slices of adult male mice. Bath application of CGRP produced dose-dependent potentiation of evoked excitatory postsynaptic currents (eEPSCs). This potentiation was NMDA receptor (NMDAR) independent. After application of CGRP1 receptor antagonist CGRP8-37 or BIBN 4096, CGRP produced potentiation was significantly reduced. Paired-pulse facilitation was significantly decreased by CGRP, suggesting possible presynaptic mechanisms. Consistently, bath application of CGRP significantly increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs). By contrast, amplitudes of sEPSCs and mEPSCs were not significantly affected. Finally, adenylyl cyclase subtype 1 (AC1) and protein kinase A (PKA) are critical for CGRP-produced potentiation, since both selective AC1 inhibitor NB001 and the PKA inhibitor KT5720 completely blocked the potentiation. Our results provide direct evidence that CGRP contributes to synaptic potentiation in the IC, and the AC1 inhibitor NB001 may be beneficial for the treatment of migraine in the future.

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“…In light of these, pre-LTP is thought to mediates anxiety signals triggered by chronic pain, while post-LTP is related to behavioral hyperalgesia during chronic pain [57]. In a recent study, Zhuo M et al succeeded in recording pre-LTP in the insular cortex, which shared similar molecular mechanisms with ACC pre-LTP [58]. In the present study, we observed an increase in presynaptic glutamate release within aIC, suggesting the possibility of the existence of insular pre-LTP during painful CP.…”

Section: Discussionmentioning

confidence: 99%

Anterior insular cortex mediates hyperalgesia induced by chronic pancreatitis in rats

Bai

Chen

et al. 2019

Mol Brain

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Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. This study was designed to examine the role of anterior insular cortex (aIC) in the pathogenesis of hyperalgesia in a rat model of CP. CP was induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). Abdomen hyperalgesia and anxiety were assessed by von Frey filament and open field tests, respectively. Two weeks after surgery, the activation of aIC was indicated by FOS immunohistochemical staining and electrophysiological recordings. Expressions of VGluT1, NMDAR subunit NR2B and AMPAR subunit GluR1 were analyzed by immunoblottings. The regulatory roles of aIC in hyperalgesia and pain-related anxiety were detected via pharmacological approach and chemogenetics in CP rats. Our results showed that TNBS treatment resulted in long-term hyperalgesia and anxiety-like behavior in rats. CP rats exhibited increased FOS expression and potentiated excitatory synaptic transmission within aIC. CP rats also showed up-regulated expression of VGluT1, and increased membrane trafficking and phosphorylation of NR2B and GluR1 within aIC. Blocking excitatory synaptic transmission significantly attenuated abdomen mechanical hyperalgesia. Specifically inhibiting the excitability of insular pyramidal cells reduced both abdomen hyperalgesia and pain-related anxiety. In conclusion, our findings emphasize a key role for aIC in hyperalgesia and anxiety of painful CP, providing a novel insight into cortical modulation of painful CP and shedding light on aIC as a potential target for neuromodulation interventions in the treatment of CP.

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Calcium-stimulated adenylyl cyclase subtype 1 is required for presynaptic long-term potentiation in the insular cortex of adult mice

Cited by 25 publications

References 34 publications

Cortical potentiation induced by calcitonin gene-related peptide (CGRP) in the insular cortex of adult mice

Cortical potentiation induced by calcitonin gene-related peptide (CGRP) in the insular cortex of adult mice

Cortical potentiation induced by calcitonin gene-related peptide (CGRP) in the insular cortex of adult mice

Anterior insular cortex mediates hyperalgesia induced by chronic pancreatitis in rats

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