Grover Dhruv, Chen Jen-Yung, Xie Jiayun, Li Jinfang, Changeux Jean-Pierre, Greenspan Ralph J
Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA, USA.
CNRS UMR 3571, Institut Pasteur, Paris, France.
Nature. 2022 Mar;603(7900):302-308. doi: 10.1038/s41586-022-04433-6. Epub 2022 Feb 16.
Two forms of associative learning-delay conditioning and trace conditioning-have been widely investigated in humans and higher-order mammals. In delay conditioning, an unconditioned stimulus (for example, an electric shock) is introduced in the final moments of a conditioned stimulus (for example, a tone), with both ending at the same time. In trace conditioning, a 'trace' interval separates the conditioned stimulus and the unconditioned stimulus. Trace conditioning therefore relies on maintaining a neural representation of the conditioned stimulus after its termination (hence making distraction possible), to learn the conditioned stimulus-unconditioned stimulus contingency; this makes it more cognitively demanding than delay conditioning. Here, by combining virtual-reality behaviour with neurogenetic manipulations and in vivo two-photon brain imaging, we show that visual trace conditioning and delay conditioning in Drosophila mobilize R2 and R4m ring neurons in the ellipsoid body. In trace conditioning, calcium transients during the trace interval show increased oscillations and slower declines over repeated training, and both of these effects are sensitive to distractions. Dopaminergic activity accompanies signal persistence in ring neurons, and this is decreased by distractions solely during trace conditioning. Finally, dopamine D1-like and D2-like receptor signalling in ring neurons have different roles in delay and trace conditioning; dopamine D1-like receptor 1 mediates both forms of conditioning, whereas the dopamine D2-like receptor is involved exclusively in sustaining ring neuron activity during the trace interval of trace conditioning. These observations are similar to those previously reported in mammals during arousal, prefrontal activation and high-level cognitive learning.
两种关联学习形式——延迟条件作用和痕迹条件作用——已在人类和高等哺乳动物中得到广泛研究。在延迟条件作用中，非条件刺激（例如电击）在条件刺激（例如音调）的最后时刻引入，两者同时结束。在痕迹条件作用中，一个“痕迹”间隔将条件刺激和非条件刺激分开。因此，痕迹条件作用依赖于在条件刺激终止后维持其神经表征（从而使分心成为可能），以学习条件刺激 - 非条件刺激的关联性；这使得它比延迟条件作用在认知上要求更高。在这里，通过将虚拟现实行为与神经遗传学操作以及体内双光子脑成像相结合，我们表明果蝇中的视觉痕迹条件作用和延迟条件作用会调动椭球体中的R2和R4m环神经元。在痕迹条件作用中，痕迹间隔期间的钙瞬变在重复训练中显示出振荡增加和下降变慢，并且这两种效应都对分心敏感。多巴胺能活动伴随着环神经元中的信号持续存在，并且仅在痕迹条件作用期间分心会降低这种活动。最后，环神经元中的多巴胺D1样和D2样受体信号在延迟和痕迹条件作用中具有不同作用；多巴胺D1样受体1介导两种条件作用形式，而多巴胺D2样受体仅在痕迹条件作用的痕迹间隔期间参与维持环神经元活动。这些观察结果与先前在哺乳动物的觉醒、前额叶激活和高级认知学习中报道的结果相似。
