NMDA receptors contribute to synaptic transmission in anterior cingulate cortex of adult mice

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Jason LIAUW()
Journal Title:
Volume 55, Issue 04, 2003
Key Word:
glutamate;anterior cingulate cortex (ACC);pain;mouse

Abstract: Glutamatergic synapses are common excitatory chemical connections in mammalian central nervous system. At these synapses, most of baseline synaptic transmission is mediated by glutamate AMPA receptors. NMDA receptors that are sensitive to voltage-dependent magnesium blockade selectively contribute to activity-dependent synaptic plasticity. However, inhibition of NMDA receptors by systemic or local administration of NMDA receptor antagonists produced significant effects on different physiological functions that are not believed to depend on NMDA receptor related synaptic plasticity. Here we show that NMDA receptors contribute to synaptic responses in the anterior cingulate cortex (ACC), a region important for cognitive and other brain functions. The contribution of NMDA receptors became more prominent when synapses are stimulated at higher frequencies. Furthermore, at temperatures more close to physiological brain temperatures, more NMDA receptor mediated responses were recorded as compared to the room temperature. These data suggest a new function for NMDA receptors in the ACC as important postsynaptic receptors involved in synaptic transmission, in particular when cells are firing at high frequencies.

  • [1]Bliss TVP, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993;361:31-39.
  • [2]Seeburg PH. The molecular biology of mammalian glutamate receptor channels. Trends Neurosci 1993;16:359-365.
  • [3]Hollmann M, Heinemann S. Cloned glutamate receptors. Annu Rev Neurosci 1994;17:31-108.
  • [4]Huettner JE, Kerchner GA, Zhuo M. Glutamate and presynaptic control of spinal sensory transmission. Neuroscientist 2002;8:89-92.
  • [5]Sah P, Hestrin S, Nicoll RA. Tonic activation of NMDA receptors by ambient glutamate enhances excitability of neurons. Science 1989;246:815-818.
  • [6]Gil Z, Amitai Y. Adult thalamocortical transmission involves both NMDA and non NMDA receptors. J Neurophysiol 1996;76:2547-2554.
  • [7]Schiller J, Major G, Koester HJ, Schiller Y. NMDA spikes in basal dendrites of cortical pyramidal neurons. Nature 2000;404:285-289.
  • [8]Wang GD, Zhuo M. Synergistic enhancement of glutamate-mediated responses by serotonin and forskolin in adult mouse spinal dorsal horn neurons. J Neurophysiol 2002;87:732-739.
  • [9]Boyce S, Wyatt A, Webb JK, O′Donnell R, Mason G, Rigby M, Sirinathsinghji D, Hill RG, Rupniak NMJ. Selective NMDA NR2B antagonists induce antinociception without motor dysfunction: correlation with restricted localization of NR2B subunit in dorsal horn. Neuropharmacology 1999;38:611-623.
  • [10]Zhuo M. Glutamate receptors and persistent pain: target-ing forebrain NR2B subunits.Drug Discov Today 2002;7:259-267.
  • [11]Kemp JA, Kew JNC, Gill R. NMDA receptor antagonists and their potential as neuroprotective agents. In: Jonas P, Monyer H ed. Handbook of Experimental Pharmacology 141: Ionotropic Glutamate Receptors in the CNS. Springer-Verlag:Berlin, Germany. 1999, 498-527.
  • [12]Posner MI. Attention: the mechanisms of consciousness. Proc Natl Acad Sci USA 1994;91:7398-7403.
  • [13]Hutchison WD, Davis KD, Lozano AM, Tasker RR, Dostrovsky JO. Pain-related neurons in the human cingulate cortex. Nature Neuroscience 1999;2:403-405.
  • [14]Botvinick M, Nystrom LE, Fissell K, Carter CS, Cohen JD. Conflict monitoring versus selection-for-attention in anterior cingulate cortex. Nature 1999;402:179-181.
  • [15]Craig AD, Reiman EM, Evans A, Bushnell MC. Functional imaging of an illusion of pain. Nature 1996;384:258-260.
  • [16]Devinsky O, Morrell MJ, Vogt BA. Contributions of anterior cingulate cortex to behavior. Brain 1995;118:279-306.
  • [17]Shidara M, Richmond BJ. Anterior cingulated cortex: single neuronal signals related to degree of reward expectancy. Science 2002;296:1709-1711.
  • [18]Gehring WJ, Willoughby AR. The medial frontal cortex and the rapid processing of monetary gains and losses. Science 2002;295:2279-2282.
  • [19]Tang YP, Shimizu E, Dube GB, Rampon C, Kerchner GA, Zhuo M, Liu G, Tsien JZ. Genetic enhancement of learning and memory in mice. Nature 1999;401:63-69.
  • [20]Wei F, Wang GD, Kerchner GA, Kim SJ, Xu HM, Chen ZF, Zhuo, M. Genetic enhancement of inflammatory pain by forebrain NR2B overexpression. Nature Neurosci 2001;4:164-169.
  • [21]Collingridge GL, Bliss TV. Memories of NMDA receptors and LTP. Trends Neurosci 1995;18:54-56.
  • [22]Wei F, Li P, Zhuo M. Loss of synaptic depression in mammalian anterior cingulate cortex after amputation. J Neurosci 1999;19:9346-9354.
  • [23]Sah P, Nicoll RA. Mechanisms underlying potentiation of synaptic transmission in rat anterior cingulate cortex in vitro. J Physiol (Lond.) 1991;433:615-630.
  • [24]Vogt BA, Gorman ALF. Responses of cortical neurons to stimulation of corpus callosum in vitro. J Neurophysiol 1982;48:1257-1273.
  • [25]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.
  • [26]Tolle TR, Kaufmann T, Siessmeier T, Lautenbacher S, Berthele A, Munz F, Ziglgansberger W, Willoch F, Schwaiger M, Conrad B, Bertenstain P. Region-specific encoding of sensory and affective components of pain in the human brain: a positron emission tomography correlation analysis. Ann Neurol 1999;45:40-47.
  • [27]Davis KD, Taylor SJ, Crawley AP, Wood ML, Mikulis RJ. Functional MRI of pain-and attention-related activations in the human cingulate cortex. J Neurophysiol 1997;77:3370-3380.
  • [28]Derbyshire SW, Vogt BA, Jones AK. Pain and Stroop interference tasks activate separate processing modules in anterior cingulate cortex. Exp Brain Res 1998; 118:52-60.
  • [29]Lenz FA, Rios M, Zirh A, Chau D, Krauss G, Lesser RP. Painful stimuli evoke potentials recorded over the human anterior cingulate gyrus. J Neurophysiol 1998;79:2231-2234.
  • [30]Paulson PE, Minoshima S, Morrow TJ, Casey KL. Gender differences in pain perception and patterns of cerebral activation during noxious heat stimulation in humans. Pain 1998;76:223-229.
  • [31]Talbot JD, Marrett S, Evans AC, Meyer E, Bushnell MC, Duncan GH. Multiple representations of pain in human cerebral cortex. Science 1991;251:1355-1358.
  • [32]Vogt BA, Derbyshire S, Jones AK. Pain processing in four regions of human cingulate cortex localized with co-registered PET and MR imaging. Eur J Neurosci 1996;8:1461-1473.
  • [33]Koyama T, Tanaka YZ, Mikami A. Nociceptive neurons in the macaque anterior cingulate activate during anticipation of pain. Neuroreport 1998;9:2663-2667.
  • [34]Sikes RW, Vogt BA. Nociceptive neurons in area 24 of rabbit cingulate cortex. J Neurophysiol 1992;68:1720-1732.
  • [35]Traub RJ, Silva E, Gebhart GF, Solodkin A. Noxious colorectal distention induced-c-Fos protein in limbic brain structures in the rat. Neurosci Lett 1996;215:165-168.
  • [36]Pastoriza LN, Morrow TJ, Casey KL. Medial frontal cortex lesions selectively attenuate the hot plate response: possible nocifensive apraxia in the rat. Pain 1996;64:11-17.
  • [37]Lee DE, Kim SJ, Zhuo M. Comparison of behavioural responses to noxious cold and heat in mice. Brain Research 1999;845, 117-121.
  • [38]Calejesan AA, Kim SJ, Zhuo M. Descending facilitatory modulation of a behavioral nociceptive response by stimulation in the adult rat anterior cingulate cortex. European J Pain 2000;4:83-96.
  • [39]Foltz EL, White LE. Pain "relief" by frontal cingulumotomy. J Neurosurg 1962;19:89-100.
  • [40]Hurt RW, Ballantine Jr HT. Stereotactic anterior cingulate lesions for persistent pain: A report on 68 cases. Clin Neurosurg 1973;21:334-351.
  • [41]Yarnitsky D, Barron SA, Bental E. Disappearance of phantom pain after focal brain infarction. Pain 1988;32:285-287.
  • [42]Vogt BA, Skies RW, Vogt LJ. Anterior cingulate cortex and the medical pain system. In: Vogt BA, Gabriel M eds. Neurobiology of cingulate cortex and limbic thalamus: a comprehensive handbook. Boston: Birkhauser, 1993;313-344.
  • [43]Rainville P. Brain mechanisms of pain affect and pain modulation. Curr Opin Neurobiol 2002;12:195-204.
  • [44]Tanaka E, North RA. Opioid actions on rat anterior cingulate cortex neurons in vitro. J Neurosci 1994;14:1106-1113.
  • [45]Petralia RS,Wang YX,Wenthold RJ.The NMDA receptor subunits NR2A and NR2B show histological and ultrastructural localization patterns similar to those of NR1. J Neurosci 1994;14:6102-6020.
  • [46]Petralia RS, Yokotani N, Wenthold RJ. Light and electron microscope distribution of the NMDA receptor subunit NMDAR1 in the rat nervous system using a selective anti-peptide antibody. J Neurosci 1994;14:667-696.
  • [47]Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 1994;12:529-540.
  • [48]Wei F, Zhuo M. Potentiation of synaptic responses in the anterior cingulate cortex following digital amputation in rat. J Physiol (Lond) 2001;532:823-833.
  • [49]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. Nature Neurosci 2002;5:573-579.
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