Nicotine exposure in vivo induces long‐lasting enhancement of NMDA receptor‐mediated currents in the hippocampus

Nicotine exposure in vivo induces long‐lasting enhancement of NMDA receptor‐mediated currents in the hippocampus
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DOI:
10.1111/j.1460-9568.2006.04714.x
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发表时间:
2006-04
影响因子:
3.4
通讯作者:
Y. Yamazaki;Yousheng Jia;R. Niu;K. Sumikawa
Y. Yamazaki;Yousheng Jia;R. Niu;K. Sumikawa
中科院分区:
医学3区
文献类型:
--
作者:
Y. Yamazaki;Yousheng Jia;R. Niu;K. Sumikawa

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通过吸烟使用尼古丁会形成持久的记忆,这些记忆会根据与之前使用尼古丁相关的环境线索而被召回。然而,构成这些持久记忆的大脑记忆系统的变化尚不清楚。 N-甲基-d-天冬氨酸受体(NMDAR)对于突触的持久修饰至关重要。在这里,我们发现体内尼古丁暴露会诱导海马体中含有 NR2B 的 NMDAR 介导的电流增强,海马体是与记忆形成相关的大脑区域。这种尼古丁效应在持续接触尼古丁期间得以维持,并伴随着 NR2B 酪氨酸磷酸化的增加。此外,在暴露于尼古丁的海马中诱导的长时程增强(LTP)被认为是学习和记忆的细胞底物,其中含有一种不依赖于蛋白质合成的长效成分。 NR2B 选择性拮抗剂可阻断 LTP 的长效成分,但不能阻断 LTP。这些结果表明,接触尼古丁提供了促进突触持久修饰的诱导的条件,这可能参与涉及尼古丁使用的记忆的形成。
The use of nicotine via cigarette smoking forms long‐lasting memories that are recalled in response to environmental cues associated with previous nicotine use. However, the changes in brain memory systems that underlie these long‐lasting memories are not well understood. The N‐methyl‐d‐aspartate receptor (NMDAR) is critical for long‐lasting modifications of synapses. Here we show that in vivo nicotine exposure induces the enhancement of NR2B‐containing NMDAR‐mediated currents in the hippocampus, a brain region associated with the formation of memories. This nicotine effect is maintained during continued nicotine exposure and is accompanied by increased tyrosine phosphorylation of NR2B. Furthermore, long‐term potentiation (LTP), which is considered to be a cellular substrate of learning and memory, induced in nicotine‐exposed hippocampi contains a protein synthesis‐independent long‐lasting component. An NR2B‐selective antagonist blocks a long‐lasting component of LTP, but not LTP. These results suggest that exposure to nicotine provides conditions that promote the induction of long‐lasting modifications of synapses, which may be involved in the formation of memories involving nicotine use.