Suppression of GABAergic neurons through D2-like receptor secures efficient conditioning in Drosophila aversive olfactory learning
Suppression of GABAergic neurons through D2-like receptor secures efficient conditioning in Drosophila aversive olfactory learning
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通过 D2 样受体抑制 GABA 能神经元可确保果蝇厌恶嗅觉学习的有效调节
DOI：
10.1073/pnas.1812342116
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发表时间：
2019
影响因子：
11.1
通讯作者：
Yan Li
中科院分区：
文献类型：
--
作者：
Mingmin Zhou;Nannan Chen;Jingsong Tian;Jianzhi Zeng;Yunpeng Zhang;Xiaofan Zhang;Jing Guo;Jinghan Sun;Yulong L;Aike Guo;Yan Li
GABA能系统在认知功能如学习和记忆中作为重要的负性调节剂，而控制该抑制系统的机制仍有待阐明。在果蝇中，GABA能前对外侧（APL）神经元介导气味辨别所必需的负反馈;然而，它们的活性通过未知的机制被学习抑制。在厌恶性嗅觉学习中，一组多巴胺能神经元在电击（ES）时被激活，并调节嗅觉学习中心蘑菇体中的Kenyon细胞（KCs）。在此我们发现，同一组DA神经元也与APL神经元形成功能性突触连接，从而通过Drosophiladopamine 2-like receptor（DD 2 R）向APL神经元发出抑制信号。敲低APL神经元中的DD 2 R或其下游分子导致行为水平的嗅觉学习受损。从体内功能成像实验中获得的结果表明，这种DD 2 R依赖的DA-APL抑制发生在气味-ES条件化过程中，并释放GABA能抑制特定于条件气味的KC。此外，APL神经元的气味反应的减少持续到后处理阶段，并且这种变化在DD 2 R敲低果蝇中也不存在。总之，我们的研究结果表明，DA-GABA抑制是必不可少的抑制条件反射过程中的GABA能抑制，以及在这个学习回路中诱导突触修饰。这种回路机制可能在跨物种的联想学习中发挥保守的作用。
The GABAergic system serves as a vital negative modulator in cognitive functions, such as learning and memory, while the mechanisms governing this inhibitory system remain to be elucidated. InDrosophila, the GABAergic anterior paired lateral (APL) neurons mediate a negative feedback essential for odor discrimination; however, their activity is suppressed by learning via unknown mechanisms. In aversive olfactory learning, a group of dopaminergic (DA) neurons is activated on electric shock (ES) and modulates the Kenyon cells (KCs) in the mushroom body, the center of olfactory learning. Here we find that the same group of DA neurons also form functional synaptic connections with the APL neurons, thereby emitting a suppressive signal to the latter throughDrosophiladopamine 2-like receptor (DD2R). Knockdown of either DD2R or its downstream molecules in the APL neurons results in impaired olfactory learning at the behavioral level. Results obtained from in vivo functional imaging experiments indicate that this DD2R-dependent DA-to-APL suppression occurs during odor-ES conditioning and discharges the GABAergic inhibition on the KCs specific to the conditioned odor. Moreover, the decrease in odor response of the APL neurons persists to the postconditioning phase, and this change is also absent in DD2R knockdown flies. Taken together, our findings show that DA-to-GABA suppression is essential for restraining the GABAergic inhibition during conditioning, as well as for inducing synaptic modification in this learning circuit. Such circuit mechanisms may play conserved roles in associative learning across species.