Laboratory of Functional Biology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki 769-2193, Japan.
J Neurosci. 2013 Jan 2;33(1):371-83. doi: 10.1523/JNEUROSCI.0679-12.2013.
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.
圆田螺能够学习味觉厌恶，并将这种学习转化为长期记忆（LTM），即条件性味觉厌恶（CTA）。先前的研究表明，在表现出 CTA 的蜗牛中，一些软体动物胰岛素相关肽（MIPs）上调。因此，我们假设 MIPs 在 CTA-LTM 巩固过程中的神经元中发挥重要作用。为了检验这一假设，我们首先观察了 MIP II 的分布，MIP II 是 MIPs 的主要肽之一，以及 MIP 受体，并确定了它们在中枢神经系统中的 mRNA 含量。MIP II 仅在脑神经节中的浅绿色细胞中观察到，而 MIP 受体分布在整个中枢神经系统中，包括口腔神经节。接下来，当我们将外源性哺乳动物胰岛素、含有 MIP 的细胞的分泌物或部分纯化的 MIPs 应用于分离的中枢神经系统时，我们观察到大脑巨细胞（CTA 的关键中间神经元）和 B1 运动神经元（口腔运动神经元）之间突触连接的长期变化（即增强）。这种突触增强被应用于分离的中枢神经系统的胰岛素受体抗体所阻断。最后，在 CTA 训练前将胰岛素受体抗体注入蜗牛体内，虽然不会阻断味觉厌恶学习的获得，但会阻断记忆巩固过程；因此，不会观察到 LTM。这些数据表明，MIPs 触发了突触连接的变化，这可能与 Lymnaea 中枢神经系统中味觉厌恶学习向 CTA-LTM 的巩固有关。
