Morielli A D, Matera E M, Kovac M P, Shrum R G, McCormack K J, Davis W J
Proc Natl Acad Sci U S A. 1986 Jun;83(12):4556-60. doi: 10.1073/pnas.83.12.4556.
Food avoidance learning in the mollusc Pleurobranchaea entails reduction in the responsiveness of key brain interneurons in the feeding neural circuitry, the paracerebral feeding command interneurons (PCNs), to the neurotransmitter acetylcholine (AcCho). Food stimuli applied to the oral veil of an untrained animal depolarize the PCNs and induce the feeding motor program (FMP). Atropine (a muscarinic cholinergic antagonist) reversibly blocks the food-induced depolarization of the PCNs, implicating AcCho as the neurotransmitter mediating food detection. AcCho applied directly to PCN somata depolarizes them, indicating that the PCN soma membrane contains AcCho receptors and induces the FMP in the isolated central nervous system preparation. The AcCho response of the PCNs is mediated by muscarinic-like receptors, since comparable depolarization is induced by muscarinic agonists (acetyl-beta-methylcholine, oxotremorine, pilocarpine), but not nicotine, and blocked by muscarinic antagonists (atropine, trifluoperazine). The nicotinic antagonist hexamethonium, however, blocked the AcCho response in four of six cases. When specimens are trained to suppress feeding behavior using a conventional food-avoidance learning paradigm (conditionally paired food and shock), AcCho applied to PCNs in the same concentration as in untrained animals causes little or no depolarization and does not initiate the FMP. Increasing the concentration of AcCho 10-100 times, however, induces weak PCN depolarization in trained specimens, indicating that learning diminishes but does not fully abolish AcCho responsiveness of the PCNs. This study proposes a cellular mechanism of long-term associative learning--namely, postsynaptic modulation of neurotransmitter responsiveness in central neurons that could apply also to mammalian species.
软体动物侧鳃海兔的食物回避学习涉及到摄食神经回路中关键脑中间神经元，即脑旁摄食指令中间神经元（PCNs），对神经递质乙酰胆碱（AcCho）的反应性降低。施加于未训练动物口膜的食物刺激会使PCNs去极化并诱发摄食运动程序（FMP）。阿托品（一种毒蕈碱胆碱能拮抗剂）可可逆地阻断食物诱导的PCNs去极化，这表明AcCho是介导食物检测的神经递质。直接施加于PCN胞体的AcCho会使其去极化，这表明PCN胞体膜含有AcCho受体，并在离体中枢神经系统制剂中诱发FMP。PCNs的AcCho反应是由类毒蕈碱受体介导的，因为毒蕈碱激动剂（乙酰-β-甲基胆碱、氧化震颤素、毛果芸香碱）可诱发类似的去极化，但尼古丁不能，且毒蕈碱拮抗剂（阿托品、三氟拉嗪）可阻断这种去极化。然而，烟碱拮抗剂六甲铵在六例中有四例阻断了AcCho反应。当使用传统的食物回避学习范式（条件性配对食物和电击）训练标本以抑制摄食行为时，以与未训练动物相同浓度施加于PCNs的AcCho几乎不会引起去极化或根本不会引起去极化，也不会启动FMP。然而，将AcCho的浓度提高10 - 100倍，会在训练后的标本中诱发微弱的PCN去极化，这表明学习会降低但不会完全消除PCNs对AcCho的反应性。本研究提出了一种长期联想学习的细胞机制——即中枢神经元中神经递质反应性的突触后调节，这也可能适用于哺乳动物。
