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. 2009 Oct 7;25(5):301. doi: 10.1007/s12264-009-0904-5

Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction of long-term potentiation in rats

大鼠前扣带皮层细胞外信号激酶参与长时程增强的诱导

Hong Cao 1, Yi-Hui Cui 2, Zhi-Qi Zhao 1, Xiao-Hua Cao 2, Yu-Qiu Zhang 1,✉
PMCID: PMC5552606  PMID: 19784086

Abstract

Objective

To explore the role of the extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) pathway in the induction of long-term potentiation (LTP) in the anterior cingulate cortex (ACC) that may be implicated in pain-related negative emotion.

Methods

LTP of field potential was recorded in ACC slice and the expressions of phospho-ERK (pERK) and phospho-CREB (pCREB) were examined using immunohistochemistry method.

Results

LTP could be induced stably in ACC slice by high frequency stimulation (2-train, 100 Hz, 1 s), while APv (an antagonist of NMDA receptor) could block the induction of LTP in the ACC, indicating that LTP in this experiment was NMDA receptor-dependent. Bath application of PD98059 (50 μmol/L), a selective MEK inhibitor, at 30 min before tetanic stimulation could completely block the induction of LTP. Moreover, the protein level of pERK in the ACC was transiently increased after LTP induction, starting at 5 min and returning to basal at 1 h after tetanic stimulation. The protein level of pCREB was also increased after LTP induction. The up-regulation in pERK and pCREB expressions could be blocked by pretreatment of PD98059. Double immunostaining showed that after LTP induction, most pERK was co-localized with pCREB.

Conclusion

NMDA receptor and ERK-CREB pathway are necessary for the induction of LTP in rat ACC and may play important roles in pain emotion.

Keywords: long-term potentiation, extracellular signal-regulated kinase, cAMP response element binding protein, anterior cingulate cortex, rat

Footnotes

These authors contribute equally to this work.

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