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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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Abolishment of cingulate potentiation in GluA1-/- mice. (A) Diagram of a slice showing the placement of a whole-cell patch recording and a stimulation electrode in the ACC. (B) These traces showing typical voltage responses to current injections of -100, 0, and 100 pA in ACC neurons from WT and GluA1-/- mice. (C) LTP was induced in ACC pyramidal neurons in WT mice (n = 13 slices/6 mice). (D) LTP was lost in ACC pyramidal neurons in GluA1-/- mice (n = 8 slices/6 mice). (C-D) The insets show averages of five EPSCs at baseline responses and 30 min after the pairing procedure (arrow). The dashed line indicates the mean basal synaptic responses.
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Figure 1: Abolishment of cingulate potentiation in GluA1-/- mice. (A) Diagram of a slice showing the placement of a whole-cell patch recording and a stimulation electrode in the ACC. (B) These traces showing typical voltage responses to current injections of -100, 0, and 100 pA in ACC neurons from WT and GluA1-/- mice. (C) LTP was induced in ACC pyramidal neurons in WT mice (n = 13 slices/6 mice). (D) LTP was lost in ACC pyramidal neurons in GluA1-/- mice (n = 8 slices/6 mice). (C-D) The insets show averages of five EPSCs at baseline responses and 30 min after the pairing procedure (arrow). The dashed line indicates the mean basal synaptic responses.

Mentions: It is evident that injuries trigger a series of plastic changes in pain-related cortical regions including the ACC [2,30-32]. Thus, the investigation of the molecular and cellular mechanisms regarding ACC plasticity provides insights into how the ACC processes and modulates sensory information. To reveal the roles of GluA1 and GluA2 subunits for synaptic potentiation in the ACC, we took genetic approach by using GluA1 and GluA2 knockout mice (GluA1-/- and GluA2-/-, respectively) in the present study. We performed whole-cell patch-clamp recordings from visually identified pyramidal neurons in layer II/III of the ACC slices from GluA1-/- mice and their wild-type (WT) mice. Fast excitatory postsynaptic currents (EPSCs) were obtained by delivering focal electrical stimulation to layer V (see Fig. 1A). In addition to visual identification, we confirmed that the recordings were performed from cortical pyramidal cells by injecting depolarizing currents into the neuron (Fig. 1B). Intrinsic membrane properties and action potential firing were compared between WT and GluA1-/- mice. No significant differences in passive or active intrinsic properties between neurons from WT (n = 11) and GluA1-/- mice (n = 10) were detected (t-test, P > 0.05). Table 1 summarizes the measurement of resting membrane potential, input resistance and action potential characteristics in WT and GluA1-/- mice.


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)

Abolishment of cingulate potentiation in GluA1-/- mice. (A) Diagram of a slice showing the placement of a whole-cell patch recording and a stimulation electrode in the ACC. (B) These traces showing typical voltage responses to current injections of -100, 0, and 100 pA in ACC neurons from WT and GluA1-/- mice. (C) LTP was induced in ACC pyramidal neurons in WT mice (n = 13 slices/6 mice). (D) LTP was lost in ACC pyramidal neurons in GluA1-/- mice (n = 8 slices/6 mice). (C-D) The insets show averages of five EPSCs at baseline responses and 30 min after the pairing procedure (arrow). The dashed line indicates the mean basal synaptic responses.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Abolishment of cingulate potentiation in GluA1-/- mice. (A) Diagram of a slice showing the placement of a whole-cell patch recording and a stimulation electrode in the ACC. (B) These traces showing typical voltage responses to current injections of -100, 0, and 100 pA in ACC neurons from WT and GluA1-/- mice. (C) LTP was induced in ACC pyramidal neurons in WT mice (n = 13 slices/6 mice). (D) LTP was lost in ACC pyramidal neurons in GluA1-/- mice (n = 8 slices/6 mice). (C-D) The insets show averages of five EPSCs at baseline responses and 30 min after the pairing procedure (arrow). The dashed line indicates the mean basal synaptic responses.
Mentions: It is evident that injuries trigger a series of plastic changes in pain-related cortical regions including the ACC [2,30-32]. Thus, the investigation of the molecular and cellular mechanisms regarding ACC plasticity provides insights into how the ACC processes and modulates sensory information. To reveal the roles of GluA1 and GluA2 subunits for synaptic potentiation in the ACC, we took genetic approach by using GluA1 and GluA2 knockout mice (GluA1-/- and GluA2-/-, respectively) in the present study. We performed whole-cell patch-clamp recordings from visually identified pyramidal neurons in layer II/III of the ACC slices from GluA1-/- mice and their wild-type (WT) mice. Fast excitatory postsynaptic currents (EPSCs) were obtained by delivering focal electrical stimulation to layer V (see Fig. 1A). In addition to visual identification, we confirmed that the recordings were performed from cortical pyramidal cells by injecting depolarizing currents into the neuron (Fig. 1B). Intrinsic membrane properties and action potential firing were compared between WT and GluA1-/- mice. No significant differences in passive or active intrinsic properties between neurons from WT (n = 11) and GluA1-/- mice (n = 10) were detected (t-test, P > 0.05). Table 1 summarizes the measurement of resting membrane potential, input resistance and action potential characteristics in WT and GluA1-/- mice.

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