Enhanced quantal release of excitatory transmitter in anterior cingulate cortex of adult mice with chronic pain
Tóm tắt
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.
Tài liệu tham khảo
Devinsky O, Morrell MJ, Vogt BA: Contributions of anterior cingulate cortex to behaviour. Brain 1995, 118: 279–306.
Zhuo M: A synaptic model for pain: long-term potentiation in the anterior cingulate cortex. Mol Cells 2007, 23: 259–271.
Zhuo M: Molecular mechanisms of pain in the anterior cingulate cortex. J Neurosci Res 2006, 84: 927–933.
Zhuo M: Central plasticity in pathological pain. Novartis Found Symp 2004, 261: 132–145. discussion 145–154.
Frankland PW, Bontempi B, Talton LE, Kaczmarek L, Silva AJ: The involvement of the anterior cingulate cortex in remote contextual fear memory. Science 2004, 304: 881–883.
Wei F, Qiu CS, Liauw J, Robinson DA, Ho N, Chatila T, Zhuo M: Calcium calmodulin-dependent protein kinase IV is required for fear memory. Nat Neurosci 2002, 5: 573–579.
Xu H, Wu LJ, Wang H, Zhang X, Vadakkan KI, Kim SS, Steenland HW, Zhuo M: Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex. J Neurosci 2008, 28: 7445–7453.
Zhao MG, Toyoda H, Lee YS, Wu LJ, Ko SW, Zhang XH, Jia Y, Shum F, Xu H, Li BM, et al.: Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Neuron 2005, 47: 859–872.
Zhuo M: Cortical excitation and chronic pain. Trends Neurosci 2008, 31: 199–207.
Davis KD, Pope GE, Crawley AP, Mikulis DJ: Neural correlates of prickle sensation: a percept-related fMRI study. Nat Neurosci 2002, 5: 1121–1122.
Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC: Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 1997, 277: 968–971.
Singer T, Seymour B, O'Doherty J, Kaube H, Dolan RJ, Frith CD: Empathy for pain involves the affective but not sensory components of pain. Science 2004, 303: 1157–1162.
Wager TD, Rilling JK, Smith EE, Sokolik A, Casey KL, Davidson RJ, Kosslyn SM, Rose RM, Cohen JD: Placebo-induced changes in FMRI in the anticipation and experience of pain. Science 2004, 303: 1162–1167.
Wu LJ, Toyoda H, Zhao MG, Lee YS, Tang J, Ko SW, Jia YH, Shum FW, Zerbinatti CV, Bu G, et al.: Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. J Neurosci 2005, 25: 11107–11116.
Zhao MG, Ko SW, Wu LJ, Toyoda H, Xu H, Quan J, Li J, Jia Y, Ren M, Xu ZC, Zhuo M: Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain. J Neurosci 2006, 26: 8923–8930.
Zucker RS, Regehr WG: Short-term synaptic plasticity. Annu Rev Physiol 2002, 64: 355–405.
Wang XL, Zhang HM, Chen SR, Pan HL: Altered synaptic input and GABAB receptor function in spinal superficial dorsal horn neurons in rats with diabetic neuropathy. J Physiol 2007, 579: 849–861.
Glavinovic MI: Mechanisms shaping fast excitatory postsynaptic currents in the central nervous system. Neural Comput 2002, 14: 1–19.
Bekkers JM, Stevens CF: Presynaptic mechanism for long-term potentiation in the hippocampus. Nature 1990, 346: 724–729.
Zucker RS: Short-term synaptic plasticity. Annu Rev Neurosci 1989, 12: 13–31.
Wei F, Qiu CS, Kim SJ, Muglia L, Maas JW, Pineda VV, Xu HM, Chen ZF, Storm DR, Muglia LJ, Zhuo M: Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases. Neuron 2002, 36: 713–726.
Randic M: Plasticity of excitatory synaptic transmission in the spinal cord dorsal horn. Prog Brain Res 1996, 113: 463–506.
Yamashita T, Ishikawa T, Takahashi T: Developmental increase in vesicular glutamate content does not cause saturation of AMPA receptors at the calyx of held synapse. J Neurosci 2003, 23: 3633–3638.
Zucker RS: Changes in the statistics of transmitter release during facilitation. J Physiol 1973, 229: 787–810.
He L, Wu LG: The debate on the kiss-and-run fusion at synapses. Trends Neurosci 2007, 30: 447–455.
Vadakkan KI, Jia YH, Zhuo M: A behavioral model of neuropathic pain induced by ligation of the common peroneal nerve in mice. J Pain 2005, 6: 747–756.
Xu H, Wu LJ, Zhao MG, Toyoda H, Vadakkan KI, Jia Y, Pinaud R, Zhuo M: Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate receptors in spinal substantia gelatinosa. Mol Pain 2006, 2: 29.
Wu LJ, Ko SW, Toyoda H, Zhao MG, Xu H, Vadakkan KI, Ren M, Knifed E, Shum F, Quan J, et al.: Increased anxiety-like behavior and enhanced synaptic efficacy in the amygdala of GluR5 knockout mice. PLoS ONE 2007, 2: e167.