The extracellular signal-regulated kinase cascade is required for NMDA receptor-independent LTP in area CA1 but not area CA3 of the hippocampus
The extracellular signal-regulated kinase cascade is required for NMDA receptor-independent LTP in area CA1 but not area CA3 of the hippocampus
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DOI：
10.1523/jneurosci.20-09-03057.2000
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发表时间：
2000-05-01
影响因子：
5.3
通讯作者：
Klann, E
中科院分区：
文献类型：
--
作者：
Kanterewicz, BI;Urban, NN;Klann, E
细胞外信号调节激酶（ERK）的激活已被证明是NMDA受体依赖性长时程增强（LTP）所必需的。我们研究了ERK在三种形式的NMDA受体非依赖性LTP中的作用：超高频刺激诱导的LTP（200 Hz-LTP），K+通道阻断剂四乙铵（TEA）诱导的LTP（TEA-LTP）和苔藓纤维（MF）LTP（MF-LTP）。我们发现在200 Hz-LTP和TEA-LTP诱导后，ERK在CA 1区被激活，并且这种激活需要通过电压门控Ca 2+通道的Ca 2+内流。用PD 098059或U 0126抑制ERK信号级联可阻止CA 1区200 Hz-LTP和TEA-LTP的诱导。相比之下，PD 098059和U 0126都不能阻止由短或长串高频刺激诱导的CA 3区MF-LTP。U 0126也不能阻止毛喉素诱导的CA 3区增强。然而，与毛喉素，cAMP依赖性蛋白激酶（PKA）级联的激活剂，孵育的切片，导致在CA 3区的活性ERK和cAMP反应元件结合蛋白（CREB）磷酸化的增加。毛喉素诱导的活性ERK的增加被U 0126抑制，而CREB磷酸化的增加则没有，这表明在CA 3区PKA级联没有通过ERK与CREB磷酸化偶联。总体而言，我们的观察表明，ERK信号级联的激活是必要的NMDA受体独立的LTP在CA 1区，但不是在CA 3区，并建议在这些海马亚区的NMDA受体独立的LTP的信号级联的分歧。
Activation of extracellular signal-regulated kinase (ERK) has been shown to be necessary for NMDA receptor-dependent long-term potentiation (LTP). We studied the role of ERK in three forms of NMDA receptor-independent LTP: LTP induced by very high-frequency stimulation (200 Hz-LTP), LTP induced by the K+ channel blocker tetraethylammonium (TEA) (TEA-LTP), and mossy fiber (MF) LTP (MF-LTP). We found that ERK was activated in area CA1 after the induction of both 200 Hz-LTP and TEA-LTP and that this activation required the influx of Ca2+ through voltage-gated Ca2+ channels. Inhibition of the ERK signaling cascade with either PD 098059 or U0126 prevented the induction of both 200 Hz-LTP and TEA-LTP in area CA1. In contrast, neither PD 098059 nor U0126 prevented MF-LTP in area CA3 induced by either brief or long trains of high-frequency stimulation. U0126 also did not prevent forskolin-induced potentiation in area CA3. However, incubation of slices with forskolin, an activator of the cAMP-dependent protein kinase (PKA) cascade, did result in increases in active ERK and cAMP response element-binding protein (CREB) phosphorylation in area CA3. The forskolin-induced increase in active ERK was inhibited by U0126, whereas the increase in CREB phosphorylation was not, which suggests that in area CA3 the PKA cascade is not coupled to CREB phosphorylation via ERK. Overall, our observations indicate that activation of the ERK signaling cascade is necessary for NMDA receptor-independent LTP in area CA1 but not in area CA3 and suggest a divergence in the signaling cascades underlying NMDA receptor-independent LTP in these hippocampal subregions.