Involvement of Insulin-Like Peptide in Long-Term Synaptic Plasticity and Long-Term Memory of the Pond Snail Lymnaea stagnalis

Involvement of Insulin-Like Peptide in Long-Term Synaptic Plasticity and Long-Term Memory of the Pond Snail Lymnaea stagnalis
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DOI:
10.1523/jneurosci.0679-12.2013
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发表时间:
2013-01-02
影响因子:
5.3
通讯作者:
Ito, Etsuro
Ito, Etsuro
中科院分区:
医学1区
文献类型:
--
作者:
Murakami, Jun;Okada, Ryuichi;Ito, Etsuro

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塘螺(lynaea stagnation)能够学习味觉厌恶,并将这种学习巩固为长期记忆(LTM),即条件性味觉厌恶(CTA)。先前的研究表明,一些软体动物胰岛素相关肽(MIPs)在表现CTA的蜗牛中上调。因此,我们假设mip在CTA-LTM巩固过程的神经元中起重要作用。为了验证这一假设,我们首先观察了MIP II (MIP的主要肽)和MIP受体的分布,并确定了它们在中枢神经系统中mrna的数量。MIP II仅在大脑神经节的浅绿色细胞中观察到,但MIP受体分布在整个中枢神经系统,包括颊神经节。接下来,当我们将外源性哺乳动物胰岛素、含有mip的细胞或部分纯化的mip的分泌物应用于分离的中枢神经系统时,我们观察到脑巨细胞(CTA的关键中间神经元)和B1运动神经元(颊运动神经元)之间突触连接的长期变化(即增强)。这种突触增强被胰岛素受体抗体应用于分离的中枢神经系统阻断。最后,在CTA训练前向蜗牛体内注射胰岛素受体抗体,在不阻断味觉厌恶学习习得的同时,阻断了记忆巩固过程;因此,未观察到LTM。这些数据表明,mip触发突触连通性的变化,这可能与味觉厌恶学习在淋巴中枢神经系统中的CTA-LTM巩固有关。
The pond snail Lymnaea stagnalis is capable of learning taste aversion and consolidating this learning into long-term memory (LTM) that is called conditioned taste aversion (CTA). Previous studies showed that some molluscan insulin-related peptides (MIPs) were upregulated in snails exhibiting CTA. We thus hypothesized that MIPs play an important role in neurons underlying the CTA-LTM consolidation process. To examine this hypothesis, we first observed the distribution of MIP II, a major peptide of MIPs, and MIP receptor and determined the amounts of their mRNAs in the CNS. MIP II was only observed in the light green cells in the cerebral ganglia, but the MIP receptor was distributed throughout the entire CNS, including the buccal ganglia. Next, when we applied exogenous mammalian insulin, secretions from MIP-containing cells or partially purified MIPs, to the isolated CNS, we observed a long-term change in synaptic efficacy (i.e., enhancement) of the synaptic connection between the cerebral giant cell (a key interneuron for CTA) and the B1 motor neuron (a buccal motor neuron). This synaptic enhancement was blocked by application of an insulin receptor antibody to the isolated CNS. Finally, injection of the insulin receptor antibody into the snail before CTA training, while not blocking the acquisition of taste aversion learning, blocked the memory consolidation process; thus, LTM was not observed. These data suggest that MIPs trigger changes in synaptic connectivity that may be correlated with the consolidation of taste aversion learning into CTA-LTM in the Lymnaea CNS.