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

Published on Mar 9, 2020in Molecular Brain4.686
· DOI :10.1186/S13041-020-00580-X
Yinglu Liu1
Estimated H-index: 1
(Xi'an Jiaotong University),
Qi-Yu Chen6
Estimated H-index: 6
(Xi'an Jiaotong University)
+ 3 AuthorsMin Zhuo89
Estimated H-index: 89
(Xi'an Jiaotong University)
Sources
Abstract
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.
📖 Papers frequently viewed together
11 Citations
6 Authors (Yuya Okutsu, ..., Fusao Kato)
17 Citations
83 Citations
References42
Newest
#1Min Zhuo (U of T: University of Toronto)H-Index: 1
Adult brain structures such as the hippocampus are highly plastic to learning and gaining new experiences. Recent studies reveal that cortical areas that respond to sensory noxious stimuli (stimuli that cause pain in humans) are also highly plastic, like the learning-related hippocampus. Long-term potentiation (LTP), a key cellular model for learning and memory, is reported in the anterior cingulate cortex (ACC) and insular cortex (IC), two key cortical areas for pain perception. ACC and IC LTP ...
9 CitationsSource
#1Min Zhuo (Xi'an Jiaotong University)H-Index: 89
Abstract Increasing evidence consistently indicates that cortical mechanisms play important roles in chronic pain and its emotional disorders. Central synapses, especially excitatory synapses, are undergoing long-term memory-like plastic changes after peripheral injury. These changes not only occur at the single synaptic level, but also take place at cortical and subcortical circuits. Consequently, neuronal responses to peripheral sensory stimuli, or even to sensory inputs triggered by normal ph...
10 CitationsSource
#1Hui-Hui Miao (Xi'an Jiaotong University)H-Index: 2
#2Xu-Hui Li (Xi'an Jiaotong University)H-Index: 13
Last. Min Zhuo (Xi'an Jiaotong University)H-Index: 89
view all 4 authors...
: Recent studies indicate that presynaptic long-term potentiation in the anterior cingulate cortex may contribute to chronic pain-related anxiety. In addition to the anterior cingulate cortex, the insular cortex has also been indicated in chronic pain and its related emotional disorders. In the present study, we used a 64-channel multielectrode dish (MED64) system to record pre-long-term potentiation in the insular cortex. We showed that low-frequency stimulation paired with a GluK1-containing k...
12 CitationsSource
#1Lars Edvinsson (Lund University)H-Index: 115
#2Karin Warfvinge (Lund University)H-Index: 27
PremiseThe brain and the sensory nervous system contain a rich supply of calcitonin gene-related peptide (CGRP) and CGRP receptor components. Clinical studies have demonstrated a correlation between CGRP release and acute migraine headache that led to the development of CGRP-specific drugs that either abort acute attacks of migraine (gepants) or are effective as prophylaxis (antibodies). However, there is still much discussion concerning the site of action of these drugs.ProblemHere we describe ...
48 CitationsSource
#1Xu-Hui Li (Xi'an Jiaotong University)H-Index: 13
#2Takanori Matsuura (U of T: University of Toronto)H-Index: 3
Last. Min Zhuo (Xi'an Jiaotong University)H-Index: 89
view all 5 authors...
The neuropeptide of calcitonin gene-related peptide (CGRP) plays critical roles in chronic pain, especially in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP ...
14 CitationsSource
#1Lars Jacob StovnerH-Index: 73
#2Emma NicholsH-Index: 28
Last. Christopher J L MurrayH-Index: 220
view all 53 authors...
Summary Background Through the Global Burden of Diseases, Injuries, and Risk Factors (GBD) studies, headache has emerged as a major global public health concern. We aimed to use data from the GBD 2016 study to provide new estimates for prevalence and years of life lived with disability (YLDs) for migraine and tension-type headache and to present the methods and results in an accessible way for clinicians and researchers of headache disorders. Methods Data were derived from population-based cross...
444 CitationsSource
Calcitonin gene-related peptide (CGRP) is a promiscuous peptide, similar to many other members of the calcitonin family of peptides. The potential of CGRP to act on many different receptors with differing affinities and efficacies makes deciphering the signalling from the CGRP receptor a challenging task for researchers.
17 CitationsSource
#1Richard D. Palmiter (UW: University of Washington)H-Index: 161
The parabrachial nucleus (PBN), which is located in the pons and is dissected by one of the major cerebellar output tracks, is known to relay sensory information (visceral malaise, taste, temperature, pain, itch) to forebrain structures including the thalamus, hypothalamus, and extended amygdala. The availability of mouse lines expressing Cre recombinase selectively in subsets of PBN neurons and viruses for Cre-dependent gene expression is beginning to reveal the connectivity and functions of PB...
144 CitationsSource
#1Carlos A. Campos (UW: University of Washington)H-Index: 5
#2Anna J Bowen (UW: University of Washington)H-Index: 6
Last. Richard D. Palmiter (UW: University of Washington)H-Index: 161
view all 4 authors...
Single-cell recordings show that CGRP-expressing neurons in the parabrachial nucleus in mice respond to both noxious stimuli and signals of feeding satiety.
122 CitationsSource
#1Timothy J. Steiner (Imperial College London)H-Index: 65
#2Lars Jacob Stovner (NTNU: Norwegian University of Science and Technology)H-Index: 73
Last. Zaza Katsarava (University of Duisburg-Essen)H-Index: 62
view all 5 authors...
222 CitationsSource
Cited By4
Newest
#1Dake Huang (UI: University of Iowa)H-Index: 1
#2Fillan Grady (UI: University of Iowa)H-Index: 4
Last. Joel C. Geerling (UI: University of Iowa)H-Index: 25
view all 5 authors...
The parabrachial nucleus (PB) is composed of glutamatergic neurons at the midbrain-hindbrain junction. These neurons form many subpopulations, one of which expresses Calca, which encodes the neuropeptide calcitonin gene-related peptide (CGRP). This Calca-expressing subpopulation has been implicated in a variety of homeostatic functions, but the overall distribution of Calca-expressing neurons in this region remains unclear. Also, while previous studies in rats and mice have identified output pro...
1 CitationsSource
#1Sachie Matsumura (Nihon University)
#2Kiyofumi Yamamoto (Nihon University)H-Index: 9
Last. Masayuki Kobayashi (Nihon University)H-Index: 25
view all 9 authors...
Abstract Substance P (SP) regulates inhibitory synaptic transmission mediated by GABAA receptors in the cerebral cortex; however, SP-mediated regulation of excitatory synaptic transmission remains poorly understood. We performed whole-cell patch-clamp recordings from pyramidal neurons to examine the effects of SP on excitatory postsynaptic currents (EPSCs) mediated via AMPA receptors in the insular cortex (IC), which is involved in nociceptive information processing. First, EPSCs evoked by minim...
1 CitationsSource
#1Levi P. Sowers (UI: University of Iowa)H-Index: 10
#2Mengya Wang (UI: University of Iowa)H-Index: 2
Last. Andrew F. RussoH-Index: 46
view all 10 authors...
OBJECTIVE A hallmark of migraine is photophobia. In mice, photophobia-like behavior is induced by calcitonin gene-related peptide (CGRP), a neuropeptide known to be a key player in migraine. In this study, we sought to identify sites within the brain from which CGRP could induce photophobia. DESIGN We focused on the posterior thalamic region, which contains neurons responsive to both light and dural stimulation and has CGRP binding sites. We probed this area with both optogenetic stimulation and...
2 CitationsSource
#1Xu-Hui LiH-Index: 13
#2Qi-Yu Chen (Xi'an Jiaotong University)H-Index: 6
Last. Min Zhuo (Xi'an Jiaotong University)H-Index: 89
view all 3 authors...
Chronic pain is a major health problem and the effective treatment for chronic pain is still lacking. The recent crisis created by the overuse of opioids for pain treatment has clearly shown the need for non-addictive novel pain medicine. Conventional pain medicines usually inhibit peripheral nociceptive transmission and reduce central transmission, especially pain-related excitatory transmission. For example, both opioids and gabapentin produce analgesic effects by inhibiting the release of exc...
9 CitationsSource