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Roles of the AMPA receptor subunit GluA1 but not GluA2 in synaptic potentiation and activation of ERK in the anterior cingulate cortex.

Toyoda H, Zhao MG, Ulzhöfer B, Wu LJ, Xu H, Seeburg PH, Sprengel R, Kuner R, Zhuo M - Mol Pain (2009)

Bottom Line: Glutamate N-methyl D-aspartate (NMDA) receptors in the ACC are critical for the induction of LTP, including both NR2A and NR2B subunits.However, cellular and molecular mechanisms for the expression of ACC LTP have been less investigated.Our results demonstrate that AMPA receptor subunit GluA1 is a key mechanism for the expression of ACC LTP and inflammation-induced long-term plastic changes in the ACC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, University of Toronto Centre for the Study of Pain, 1 King's College Circle, Ontario, Canada. hiroki.toyoda@utoronto.ca

ABSTRACT
Cortical areas including the anterior cingulate cortex (ACC) are important for pain and pleasure. Recent studies using genetic and physiological approaches have demonstrated that the investigation of basic mechanism for long-term potentiation (LTP) in the ACC may reveal key cellular and molecular mechanisms for chronic pain in the cortex. Glutamate N-methyl D-aspartate (NMDA) receptors in the ACC are critical for the induction of LTP, including both NR2A and NR2B subunits. However, cellular and molecular mechanisms for the expression of ACC LTP have been less investigated. Here, we report that the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit, GluA1 but not GluA2 contributes to LTP in the ACC using genetic manipulated mice lacking GluA1 or GluA2 gene. Furthermore, GluA1 knockout mice showed decreased extracellular signal-regulated kinase (ERK) phosphorylation in the ACC in inflammatory pain models in vivo. Our results demonstrate that AMPA receptor subunit GluA1 is a key mechanism for the expression of ACC LTP and inflammation-induced long-term plastic changes in the ACC.

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ERK phosphorylation in the ACC with inflammatory-relayed pain in WT and GluA1-/- mice. (A) ERK immunoreactivity of control, and 10 min after formalin injection or 30 min after CFA injection in control (WT, top panel) and GluA1-/- mice (lower panel). (B) Quantitative summary of ERK immunoreactivity in control and GluA1-/- mice.
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Figure 8: ERK phosphorylation in the ACC with inflammatory-relayed pain in WT and GluA1-/- mice. (A) ERK immunoreactivity of control, and 10 min after formalin injection or 30 min after CFA injection in control (WT, top panel) and GluA1-/- mice (lower panel). (B) Quantitative summary of ERK immunoreactivity in control and GluA1-/- mice.

Mentions: Given the importance of both ERK and GluA1-containing AMPA receptors in plasticity phenomena in the ACC, we asked whether AMPA receptors could act upstream of nociceptive activity-evoked activation of ERK1/2 in the cortex. Phosphorylation of ERK1/2 in neurons of the ACC induced by intraplantar injection of either formalin or CFA was significantly decreased in GluA1-/- mice in comparison with their WT mice (see Fig. 8A for typical example and Fig. 8B for summary of densitometric analysis). In particular, dendrites of cortical neurons were rarely immunoreactive for pERK1/2 in formalin- or CFA-injected GluA1-/- mice. In contrast, nociceptive activity-evoked ERK1/2 phosphorylation of ERK1/2 remained intact in the ACC of GluA2-/- mice, as compared to WTCD1 mice (not shown).


Roles of the AMPA receptor subunit GluA1 but not GluA2 in synaptic potentiation and activation of ERK in the anterior cingulate cortex.

Toyoda H, Zhao MG, Ulzhöfer B, Wu LJ, Xu H, Seeburg PH, Sprengel R, Kuner R, Zhuo M - Mol Pain (2009)

ERK phosphorylation in the ACC with inflammatory-relayed pain in WT and GluA1-/- mice. (A) ERK immunoreactivity of control, and 10 min after formalin injection or 30 min after CFA injection in control (WT, top panel) and GluA1-/- mice (lower panel). (B) Quantitative summary of ERK immunoreactivity in control and GluA1-/- mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2734546&req=5

Figure 8: ERK phosphorylation in the ACC with inflammatory-relayed pain in WT and GluA1-/- mice. (A) ERK immunoreactivity of control, and 10 min after formalin injection or 30 min after CFA injection in control (WT, top panel) and GluA1-/- mice (lower panel). (B) Quantitative summary of ERK immunoreactivity in control and GluA1-/- mice.
Mentions: Given the importance of both ERK and GluA1-containing AMPA receptors in plasticity phenomena in the ACC, we asked whether AMPA receptors could act upstream of nociceptive activity-evoked activation of ERK1/2 in the cortex. Phosphorylation of ERK1/2 in neurons of the ACC induced by intraplantar injection of either formalin or CFA was significantly decreased in GluA1-/- mice in comparison with their WT mice (see Fig. 8A for typical example and Fig. 8B for summary of densitometric analysis). In particular, dendrites of cortical neurons were rarely immunoreactive for pERK1/2 in formalin- or CFA-injected GluA1-/- mice. In contrast, nociceptive activity-evoked ERK1/2 phosphorylation of ERK1/2 remained intact in the ACC of GluA2-/- mice, as compared to WTCD1 mice (not shown).

Bottom Line: Glutamate N-methyl D-aspartate (NMDA) receptors in the ACC are critical for the induction of LTP, including both NR2A and NR2B subunits.However, cellular and molecular mechanisms for the expression of ACC LTP have been less investigated.Our results demonstrate that AMPA receptor subunit GluA1 is a key mechanism for the expression of ACC LTP and inflammation-induced long-term plastic changes in the ACC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, University of Toronto Centre for the Study of Pain, 1 King's College Circle, Ontario, Canada. hiroki.toyoda@utoronto.ca

ABSTRACT
Cortical areas including the anterior cingulate cortex (ACC) are important for pain and pleasure. Recent studies using genetic and physiological approaches have demonstrated that the investigation of basic mechanism for long-term potentiation (LTP) in the ACC may reveal key cellular and molecular mechanisms for chronic pain in the cortex. Glutamate N-methyl D-aspartate (NMDA) receptors in the ACC are critical for the induction of LTP, including both NR2A and NR2B subunits. However, cellular and molecular mechanisms for the expression of ACC LTP have been less investigated. Here, we report that the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit, GluA1 but not GluA2 contributes to LTP in the ACC using genetic manipulated mice lacking GluA1 or GluA2 gene. Furthermore, GluA1 knockout mice showed decreased extracellular signal-regulated kinase (ERK) phosphorylation in the ACC in inflammatory pain models in vivo. Our results demonstrate that AMPA receptor subunit GluA1 is a key mechanism for the expression of ACC LTP and inflammation-induced long-term plastic changes in the ACC.

Show MeSH
Related in: MedlinePlus