Centre de Recherches sur la Cognition Animale, UMR 5169 CNRS UPS, 118 route de Narbonne 31062 Toulouse cedex, France.
Adv Exp Med Biol. 2010;683:97-115. doi: 10.1007/978-1-4419-6445-8_9.
Acetylcholine is the most abundant excitatory neurotransmitter in the insect brain and the most numerous acetylcholine receptors are the nicotinic ones (nAChRs). The genome sequencing of diverse insect species has demonstrated the existence of at least 10 nAChR genes coding for alpha and beta subunits, suggesting the existence in the insect CNS of several subtypes ofnAChRs whose molecular composition and pharmacological properties are still unknown. Insect nAChRs have given rise to an abundance of literature about their sensitivity to neonicotinoid insecticides but only limited data are available on the functional role of nAChRs in insect cognitive functions. The data we have collected on honeybees are the only data that shed light on the role of nAChRs in learning and memory processes. The behavioral response of proboscis extension (PER), which appears when the honeybee perceives sugar, was used to quantify learning and memory performances in associative and non-associative learning procedures. Habituation of the PER, which consists in ceasing to respond to sucrose upon repetitive antennal sucrose stimulation, was facilitated by the injection into the brain of one of the nicotinic antagonists mecamylamine, alpha-bungarotoxin (alpha-BGT) or methyllycaconitine (MLA). Pavlovian associative protocol was used to condition the PER to olfactory or tactile stimulus after single- or multiple-trial training. Localized brain injections of the nicotinic antagonist mecamylamine were performed before or after one-trial olfactory learning in the mushroom bodies (MB), the integrative structures of the insect brain. The results showed that the calical input structures of the MB are necessary for the acquisition processes and the output a-lobe regions are involved in retrieval processes. Brain injection of one of the three nicotinic antagonists mecamylamine, alpha-BGT and MLA was combined with single- and multiple-trial olfactory and tactile learning and memory performances were evaluated at long- or short-term intervals. Mecamylamine impaired the acquisition of one-trial learning and the retrieval of information, regardless of the number of trials during training and the learning modality (olfactory or tactile cues used as conditioned stimulus). Memory performance evaluated at long-term intervals was decreased by injection of alpha-BGT and MLA in multiple-trial olfactory and tactile experiments. We conclude from these results that at least two subtypes of nAChRs exist in the honeybee brain. The alpha-BGT-sensitive nAChRs are necessary for the formation of long-term memory and the alpha-BGT-insensitive nAChRs are involved in one-trial acquisition and in retrieval processes. The hypothesis is put forward that multiple-trial associative learning triggers activation of the alpha-BGT-sensitive nAChRs that, in turn, activate intracellular events leading to LTM formation.
乙酰胆碱是昆虫脑中最丰富的兴奋性神经递质，而数量最多的乙酰胆碱受体是烟碱型乙酰胆碱受体（nAChRs）。对多种昆虫物种的基因组测序表明，至少存在 10 种编码α和β亚基的 nAChR 基因，这表明在昆虫中枢神经系统中存在几种亚型的 nAChRs，但其分子组成和药理学特性尚不清楚。昆虫 nAChRs 产生了大量关于它们对新烟碱类杀虫剂敏感性的文献，但关于 nAChRs 在昆虫认知功能中的功能作用的可用数据非常有限。我们在蜜蜂身上收集的数据是唯一能够阐明 nAChRs 在学习和记忆过程中作用的数据集。当蜜蜂感知到糖时，出现的伸喙（PER）行为反应被用来量化联想和非联想学习过程中的学习和记忆表现。PER 的习惯化，即当重复用触角刺激蔗糖时停止对蔗糖的反应，通过向大脑中注射烟碱型拮抗剂美加明、α-银环蛇毒素（alpha-BGT）或甲基lycaconitine（MLA）来促进。巴甫洛夫联想协议被用来在单或多试训练后将 PER 条件到嗅觉或触觉刺激。在蘑菇体（MB）中进行了局部脑内注射烟碱型拮抗剂美加明，然后在一次嗅觉学习后进行了单试或多试学习。结果表明，MB 的钙输入结构对于获得过程是必要的，而输出 a-叶区参与检索过程。在单试和多试嗅觉和触觉学习和记忆表现中，将三种烟碱型拮抗剂之一美加明、alpha-BGT 和 MLA 进行脑内注射，并在长期或短期间隔评估。美加明损害了单次学习的获得和信息的检索，无论训练过程中的试验次数和学习方式（作为条件刺激的嗅觉或触觉线索）如何。在多试嗅觉和触觉实验中，alpha-BGT 和 MLA 的注射降低了长期记忆的表现。从这些结果中我们得出结论，在蜜蜂脑中至少存在两种亚型的 nAChRs。alpha-BGT 敏感型 nAChRs 对于长时记忆的形成是必要的，而 alpha-BGT 不敏感型 nAChRs 参与单次获得和检索过程。提出的假设是，多试联想学习触发了 alpha-BGT 敏感型 nAChRs 的激活，进而激活了导致 LTM 形成的细胞内事件。
