Learning-associated activation of nuclear MAPK, CREB and Elk-1, along with Fos production, in the rat hippocampus after a one-trial avoidance learning: abolition by NMDA receptor blockade
Learning-associated activation of nuclear MAPK, CREB and Elk-1, along with Fos production, in the rat hippocampus after a one-trial avoidance learning: abolition by NMDA receptor blockade
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DOI：
10.1016/s0169-328x(99)00329-0
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发表时间：
2000-03-10
期刊：
影响因子：
--
通讯作者：
Medina, JH
中科院分区：
文献类型：
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作者：
Cammarota, M;Bevilaqua, LRM;Medina, JH
人们普遍认为，长时记忆的形成需要神经元基因的表达、蛋白质的合成和突触接触的重塑。从软体动物到哺乳动物，cAMP/PKA/CREB信号通路在LTM的建立中起着关键作用。最近，MAPK级联也参与了内存处理。在此，我们通过激活NMDA受体，为海马区PKA/CREB和MAPK/ELK-1通路参与大鼠一次回避学习记忆形成提供了证据。这项任务的学习与p44和p42、MAPKs、CREB和ELK-1的激活以及核丰富的海马区PKA和Fos蛋白催化亚单位水平的增加有关。训练后立即向海马区注射APV，这是一种选择性的谷氨酸NMDA受体阻滞剂，使动物对这一任务失去记忆，从而阻止了这些变化。此外，在对照休克的动物中没有发现任何变化。因此，大鼠的抑制性回避训练与IEG蛋白产物c-fos的增加有关，这种增加伴随着核MAPK、CREB和ELK-1的激活。NMDA受体似乎是学习过程中激活这些细胞内级联信号的必要上游步骤。(C)2000 Elsevier Science B.V.保留所有权利。
It is widely accepted that the formation of long-term memory (LTM) requires neuronal gene expression, protein synthesis and the remodeling of synaptic contacts. From mollusk to mammals, the cAMP/PKA/CREB signaling pathway has been shown to play a pivotal role in the establishment of LTM. More recently, the MAPK cascade has been also involved in memory processing. Here, we provide evidence for the participation of hippocampal PKA/CREB and MAPK/Elk-1 pathways, via activation of NMDA receptors, in memory formation of a one-trial avoidance learning in rats. Learning of this task is associated with an activation of p44 and p42, MAPKs, CREB and Elk-1, along with an increase in the levels of the catalytic subunit of PKA and Fos protein in nuclear-enriched hippocampal fractions. These changes were blocked by the immediate posttraining intra-hippocampal infusion of APV, a selective blocker of glutamate NMDA receptors, which renders the animals amnesic for this task. Moreover, no changes were found in control-shocked animals. Thus, inhibitory avoidance training in the rat is associated with an increase in the protein product of an IEG, c-fos, which occurs concomitantly with the activation of nuclear MAPK, CREB and Elk-1. NMDA receptors appear to be a necessary upstream step for the activation of these intracellular cascades during learning. (C) 2000 Elsevier Science B.V. All rights reserved.