Enhanced Quantal Release of Excitatory Transmitter in Anterior Cingulate Cortex of Adult Mice with Chronic Pain

Overview

Journal Mol Pain

Date 2009 Jan 28

PMID 19171071

Citations 36

Authors

Hiroki Toyoda

Ming-Gao Zhao

Min Zhuo

Affiliations

Soon will be listed here.

Abstract

The anterior cingulate cortex (ACC) is a forebrain structure that plays important roles in emotion, learning, memory and persistent pain. Our previous studies have demonstrated that the enhancement of excitatory synaptic transmission was induced by peripheral inflammation and nerve injury in ACC synapses. However, little information is available on their presynaptic mechanisms, since the source of the enhanced synaptic transmission could include the enhanced probability of neurotransmitter release at existing release sites and/or increases in the number of available vesicles. The present study aims to perform quantal analysis of excitatory synapses in the ACC with chronic pain to examine the source of these increases. The quantal analysis revealed that both probability of transmitter release and number of available vesicles were increased in a mouse model of peripheral inflammation, whereas only probability of transmitter release but not number of available vesicles was enhanced in a mouse model of neuropathic pain. In addition, we compared the miniature excitatory postsynaptic potentials (mEPSCs) in ACC synapses with those in other pain-related brain areas such as the amygdala and spinal cord. Interestingly, the rate and amplitude of mEPSCs in ACC synapses were significantly lower than those in the amygdala and spinal cord. Our studies provide strong evidences that chronic inflammatory pain increases both probability of transmitter release and number of available vesicles, whereas neuropathic pain increases only probability of transmitter release in the ACC synapses.

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References

Zhuo M . Central plasticity in pathological pain. Novartis Found Symp. 2004; 261:132-45. View

Wu L, Ko S, Toyoda H, Zhao M, Xu H, Vadakkan K . Increased anxiety-like behavior and enhanced synaptic efficacy in the amygdala of GluR5 knockout mice. PLoS One. 2007; 2(1):e167. PMC: 1766473. DOI: 10.1371/journal.pone.0000167. View

Davis K, Pope G, Crawley A, Mikulis D . Neural correlates of prickle sensation: a percept-related fMRI study. Nat Neurosci. 2002; 5(11):1121-2. DOI: 10.1038/nn955. View

Rainville P, Duncan G, Price D, Carrier B, Bushnell M . Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science. 1997; 277(5328):968-71. DOI: 10.1126/science.277.5328.968. View

Zhao M, Ko S, Wu L, Toyoda H, Xu H, Quan J . Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain. J Neurosci. 2006; 26(35):8923-30. PMC: 6675332. DOI: 10.1523/JNEUROSCI.2103-06.2006. View

Singer T, Seymour B, ODoherty J, Kaube H, Dolan R, Frith C . Empathy for pain involves the affective but not sensory components of pain. Science. 2004; 303(5661):1157-62. DOI: 10.1126/science.1093535. View

Zhuo M . Cortical excitation and chronic pain. Trends Neurosci. 2008; 31(4):199-207. DOI: 10.1016/j.tins.2008.01.003. View

Devinsky O, Morrell M, Vogt B . Contributions of anterior cingulate cortex to behaviour. Brain. 1995; 118 ( Pt 1):279-306. DOI: 10.1093/brain/118.1.279. View

Zhao M, Toyoda H, Lee Y, Wu L, Ko S, Zhang X . Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Neuron. 2005; 47(6):859-72. DOI: 10.1016/j.neuron.2005.08.014. View

10.

Zucker R . Short-term synaptic plasticity. Annu Rev Neurosci. 1989; 12:13-31. DOI: 10.1146/annurev.ne.12.030189.000305. View

11.

Zhuo M . A synaptic model for pain: long-term potentiation in the anterior cingulate cortex. Mol Cells. 2007; 23(3):259-71. View

12.

Randic M . Plasticity of excitatory synaptic transmission in the spinal cord dorsal horn. Prog Brain Res. 1996; 113:463-506. DOI: 10.1016/s0079-6123(08)61104-8. View

13.

Zucker R . Changes in the statistics of transmitter release during facilitation. J Physiol. 1973; 229(3):787-810. PMC: 1350563. DOI: 10.1113/jphysiol.1973.sp010167. View

14.

Wang X, Zhang H, Chen S, Pan H . Altered synaptic input and GABAB receptor function in spinal superficial dorsal horn neurons in rats with diabetic neuropathy. J Physiol. 2007; 579(Pt 3):849-61. PMC: 2151355. DOI: 10.1113/jphysiol.2006.126102. View

15.

Wager T, Rilling J, Smith E, Sokolik A, Casey K, Davidson R . Placebo-induced changes in FMRI in the anticipation and experience of pain. Science. 2004; 303(5661):1162-7. DOI: 10.1126/science.1093065. View

16.

Xu H, Wu L, Zhao M, Toyoda H, Vadakkan K, Jia Y . Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate receptors in spinal substantia gelatinosa. Mol Pain. 2006; 2:29. PMC: 1570342. DOI: 10.1186/1744-8069-2-29. View

17.

Wei F, Qiu C, Kim S, Muglia L, Maas J, Pineda V . Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases. Neuron. 2002; 36(4):713-26. DOI: 10.1016/s0896-6273(02)01019-x. View

18.

He L, Wu L . The debate on the kiss-and-run fusion at synapses. Trends Neurosci. 2007; 30(9):447-55. DOI: 10.1016/j.tins.2007.06.012. View

19.

Zucker R, Regehr W . Short-term synaptic plasticity. Annu Rev Physiol. 2002; 64:355-405. DOI: 10.1146/annurev.physiol.64.092501.114547. View

20.

Xu H, Wu L, Wang H, Zhang X, Vadakkan K, Kim S . Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex. J Neurosci. 2008; 28(29):7445-53. PMC: 3844787. DOI: 10.1523/JNEUROSCI.1812-08.2008. View