Limits...
Requirement of extracellular signal-regulated kinase/mitogen-activated protein kinase for long-term potentiation in adult mouse anterior cingulate cortex.

Toyoda H, Zhao MG, Xu H, Wu LJ, Ren M, Zhuo M - Mol Pain (2007)

Bottom Line: Moreover, we found that these two inhibitors had no effect on the maintenance of cingulate LTP.Inhibitors of c-Jun N-terminal kinase (JNK) and p38, other members of MAPK family, SP600125 and SB203850, suppressed the induction of cingulate LTP generated by the pairing protocol.Thus, our study suggests that the MAPK signaling pathway is involved in the induction of cingulate LTP and plays a critical role in physiological conditions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. hiroki.toyoda@utoronto.ca

ABSTRACT
Long-term potentiation (LTP) in the anterior cingulate cortex (ACC) is believed to be critical for higher brain functions including emotion, learning, memory and chronic pain. N-methyl-D-aspartate (NMDA) receptor-dependent LTP is well studied and is thought to be important for learning and memory in mammalian brains. As the downstream target of NMDA receptors, the extracellular signal-regulated kinase (ERK) in the mitogen-activated protein kinase (MAPK) cascade has been extensively studied for its involvement in synaptic plasticity, learning and memory in hippocampus. By contrast, the role of ERK in cingulate LTP has not been investigated. In this study, we examined whether LTP in ACC requires the activation of ERK. We found that P42/P44 MAPK inhibitors, PD98059 and U0126, suppressed the induction of cingulate LTP that was induced by presynaptic stimulation with postsynaptic depolarization (the pairing protocol). We also showed that cingulate LTP induced by two other different protocols was also blocked by PD98059. Moreover, we found that these two inhibitors had no effect on the maintenance of cingulate LTP. Inhibitors of c-Jun N-terminal kinase (JNK) and p38, other members of MAPK family, SP600125 and SB203850, suppressed the induction of cingulate LTP generated by the pairing protocol. Thus, our study suggests that the MAPK signaling pathway is involved in the induction of cingulate LTP and plays a critical role in physiological conditions.

Show MeSH

Related in: MedlinePlus

LTP induced by TBS protocol is blocked by PD98059. A: A scheme illustrating the LTP induction protocol consisting of 5 trains of burst with 4 pulses at 100 Hz, 200 ms interval, which are repeated 4 times with the interval of 10 s. B: LTP is induced by the TBS protocol. The TBS protocol induced significant LTP in the ACC of adult mice (n = 8). C: LTP is blocked by addition of PD98059 (50 μM) in the intracellular solution. Traces show averages of six EPSCs at baseline response (pre) and 30 min (post) after the TBS protocol (arrow). The dashed line indicates the mean basal synaptic response. D: Summary of the effects of PD98059 (50 μM, n = 6) on LTP induced by the TBS protocol. * P < 0.05 compared to baseline.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2245920&req=5

Figure 3: LTP induced by TBS protocol is blocked by PD98059. A: A scheme illustrating the LTP induction protocol consisting of 5 trains of burst with 4 pulses at 100 Hz, 200 ms interval, which are repeated 4 times with the interval of 10 s. B: LTP is induced by the TBS protocol. The TBS protocol induced significant LTP in the ACC of adult mice (n = 8). C: LTP is blocked by addition of PD98059 (50 μM) in the intracellular solution. Traces show averages of six EPSCs at baseline response (pre) and 30 min (post) after the TBS protocol (arrow). The dashed line indicates the mean basal synaptic response. D: Summary of the effects of PD98059 (50 μM, n = 6) on LTP induced by the TBS protocol. * P < 0.05 compared to baseline.

Mentions: Next, we induced LTP using theta-burst stimulation (TBS) [3,34] (Fig. 3A). This paradigm is thought to be physiological, since the synchronized firing patterns at similar frequencies are observed during learning in the hippocampus [35]. We found that TBS induced significant LTP in the cingulate neurons (151.8 ± 12.7%; n = 8, P < 0.05 compared with baseline response) (Fig. 3B). The induction of LTP was also blocked by 50 μM PD98059 in the intracellular solution (106.1 ± 2.6%; n = 6, P > 0.05 compared with baseline response) (Fig. 3C, D). Taken together, these results indicate that the activation of ERK in LTP induction is not dependent on specific induction paradigms.


Requirement of extracellular signal-regulated kinase/mitogen-activated protein kinase for long-term potentiation in adult mouse anterior cingulate cortex.

Toyoda H, Zhao MG, Xu H, Wu LJ, Ren M, Zhuo M - Mol Pain (2007)

LTP induced by TBS protocol is blocked by PD98059. A: A scheme illustrating the LTP induction protocol consisting of 5 trains of burst with 4 pulses at 100 Hz, 200 ms interval, which are repeated 4 times with the interval of 10 s. B: LTP is induced by the TBS protocol. The TBS protocol induced significant LTP in the ACC of adult mice (n = 8). C: LTP is blocked by addition of PD98059 (50 μM) in the intracellular solution. Traces show averages of six EPSCs at baseline response (pre) and 30 min (post) after the TBS protocol (arrow). The dashed line indicates the mean basal synaptic response. D: Summary of the effects of PD98059 (50 μM, n = 6) on LTP induced by the TBS protocol. * P < 0.05 compared to baseline.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2245920&req=5

Figure 3: LTP induced by TBS protocol is blocked by PD98059. A: A scheme illustrating the LTP induction protocol consisting of 5 trains of burst with 4 pulses at 100 Hz, 200 ms interval, which are repeated 4 times with the interval of 10 s. B: LTP is induced by the TBS protocol. The TBS protocol induced significant LTP in the ACC of adult mice (n = 8). C: LTP is blocked by addition of PD98059 (50 μM) in the intracellular solution. Traces show averages of six EPSCs at baseline response (pre) and 30 min (post) after the TBS protocol (arrow). The dashed line indicates the mean basal synaptic response. D: Summary of the effects of PD98059 (50 μM, n = 6) on LTP induced by the TBS protocol. * P < 0.05 compared to baseline.
Mentions: Next, we induced LTP using theta-burst stimulation (TBS) [3,34] (Fig. 3A). This paradigm is thought to be physiological, since the synchronized firing patterns at similar frequencies are observed during learning in the hippocampus [35]. We found that TBS induced significant LTP in the cingulate neurons (151.8 ± 12.7%; n = 8, P < 0.05 compared with baseline response) (Fig. 3B). The induction of LTP was also blocked by 50 μM PD98059 in the intracellular solution (106.1 ± 2.6%; n = 6, P > 0.05 compared with baseline response) (Fig. 3C, D). Taken together, these results indicate that the activation of ERK in LTP induction is not dependent on specific induction paradigms.

Bottom Line: Moreover, we found that these two inhibitors had no effect on the maintenance of cingulate LTP.Inhibitors of c-Jun N-terminal kinase (JNK) and p38, other members of MAPK family, SP600125 and SB203850, suppressed the induction of cingulate LTP generated by the pairing protocol.Thus, our study suggests that the MAPK signaling pathway is involved in the induction of cingulate LTP and plays a critical role in physiological conditions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. hiroki.toyoda@utoronto.ca

ABSTRACT
Long-term potentiation (LTP) in the anterior cingulate cortex (ACC) is believed to be critical for higher brain functions including emotion, learning, memory and chronic pain. N-methyl-D-aspartate (NMDA) receptor-dependent LTP is well studied and is thought to be important for learning and memory in mammalian brains. As the downstream target of NMDA receptors, the extracellular signal-regulated kinase (ERK) in the mitogen-activated protein kinase (MAPK) cascade has been extensively studied for its involvement in synaptic plasticity, learning and memory in hippocampus. By contrast, the role of ERK in cingulate LTP has not been investigated. In this study, we examined whether LTP in ACC requires the activation of ERK. We found that P42/P44 MAPK inhibitors, PD98059 and U0126, suppressed the induction of cingulate LTP that was induced by presynaptic stimulation with postsynaptic depolarization (the pairing protocol). We also showed that cingulate LTP induced by two other different protocols was also blocked by PD98059. Moreover, we found that these two inhibitors had no effect on the maintenance of cingulate LTP. Inhibitors of c-Jun N-terminal kinase (JNK) and p38, other members of MAPK family, SP600125 and SB203850, suppressed the induction of cingulate LTP generated by the pairing protocol. Thus, our study suggests that the MAPK signaling pathway is involved in the induction of cingulate LTP and plays a critical role in physiological conditions.

Show MeSH
Related in: MedlinePlus