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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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Intact NMDA receptor-mediated EPSCs in GluA1-/- mice. (A) Input-output relationships for NMDA receptor-mediated EPSCs in WT (n = 6) and GluA1-/- (n = 8) mice (left). Traces showing averages of five NMDA receptor-mediated EPSCs with input stimulation at 12 V (right). (B) I-V relationships of NMDA receptor-mediated EPSCs in WT (n = 8) and GluA1-/- (n = 8) mice (left). NMDA receptor-mediated EPSCs recorded at holding potentials from -85 mV to +55 mV in WT and GluA1-/- mice (right).
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Figure 3: Intact NMDA receptor-mediated EPSCs in GluA1-/- mice. (A) Input-output relationships for NMDA receptor-mediated EPSCs in WT (n = 6) and GluA1-/- (n = 8) mice (left). Traces showing averages of five NMDA receptor-mediated EPSCs with input stimulation at 12 V (right). (B) I-V relationships of NMDA receptor-mediated EPSCs in WT (n = 8) and GluA1-/- (n = 8) mice (left). NMDA receptor-mediated EPSCs recorded at holding potentials from -85 mV to +55 mV in WT and GluA1-/- mice (right).

Mentions: NMDA receptors are critical for the induction of LTP in the ACC [13]. To test the possibility that the deletion of GluA1 subunit affect the induction of LTP by inhibiting NMDA receptor-mediated currents, we first examined the NMDA receptor-mediated EPSCs evoked by various stimulus intensities. To record NMDA receptor-mediated EPSCs, we added CNQX (20 μM) and glycine (1 μM) in the recording solution. NMDA receptor-mediated EPSCs in the ACC pyramidal neurons remained unchanged in GluA1-/- (n = 8) mice in comparison with WT mice (n = 6, Fig. 3A, left). The rise time and decay time in NMDA receptor-mediated EPSCs with input stimulation at 12 V showed no significant difference in GluA1-/- (rise time, 19.8 ± 1.2 ms; decay time, 146.9 ± 9.3 ms, n = 8) mice in comparison with WT mice (rise time, 20.7 ± 1.2 ms; decay time, 143.2 ± 7.0 ms, n = 6) (Fig. 3A, right).


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)

Intact NMDA receptor-mediated EPSCs in GluA1-/- mice. (A) Input-output relationships for NMDA receptor-mediated EPSCs in WT (n = 6) and GluA1-/- (n = 8) mice (left). Traces showing averages of five NMDA receptor-mediated EPSCs with input stimulation at 12 V (right). (B) I-V relationships of NMDA receptor-mediated EPSCs in WT (n = 8) and GluA1-/- (n = 8) mice (left). NMDA receptor-mediated EPSCs recorded at holding potentials from -85 mV to +55 mV in WT and GluA1-/- mice (right).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Intact NMDA receptor-mediated EPSCs in GluA1-/- mice. (A) Input-output relationships for NMDA receptor-mediated EPSCs in WT (n = 6) and GluA1-/- (n = 8) mice (left). Traces showing averages of five NMDA receptor-mediated EPSCs with input stimulation at 12 V (right). (B) I-V relationships of NMDA receptor-mediated EPSCs in WT (n = 8) and GluA1-/- (n = 8) mice (left). NMDA receptor-mediated EPSCs recorded at holding potentials from -85 mV to +55 mV in WT and GluA1-/- mice (right).
Mentions: NMDA receptors are critical for the induction of LTP in the ACC [13]. To test the possibility that the deletion of GluA1 subunit affect the induction of LTP by inhibiting NMDA receptor-mediated currents, we first examined the NMDA receptor-mediated EPSCs evoked by various stimulus intensities. To record NMDA receptor-mediated EPSCs, we added CNQX (20 μM) and glycine (1 μM) in the recording solution. NMDA receptor-mediated EPSCs in the ACC pyramidal neurons remained unchanged in GluA1-/- (n = 8) mice in comparison with WT mice (n = 6, Fig. 3A, left). The rise time and decay time in NMDA receptor-mediated EPSCs with input stimulation at 12 V showed no significant difference in GluA1-/- (rise time, 19.8 ± 1.2 ms; decay time, 146.9 ± 9.3 ms, n = 8) mice in comparison with WT mice (rise time, 20.7 ± 1.2 ms; decay time, 143.2 ± 7.0 ms, n = 6) (Fig. 3A, right).

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