Drosophila Ortholog of Mammalian Immediate-Early Gene Npas4 is Specifically Responsive to Reversal Learning
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LETTER TO THE EDITOR
Drosophila Ortholog of Mammalian Immediate-Early Gene Npas4 is Specifically Responsive to Reversal Learning Tingting Liu1 • Linghan Wang1 • Qian Li1
Received: 2 February 2020 / Accepted: 2 June 2020 Ó Shanghai Institutes for Biological Sciences, CAS 2020
Dear Editor, In dynamic environments, the memory system of the brain must be able to perceive and process conflicting experiences to reach an adaptive decision. In Drosophila, in contrast to consistent experiences, conflicting experiences trigger significantly increased Rac1 activity which mediates active forgetting [1]. The ability to cope with conflicting experiences but not simple learning experiences is impaired in mutants of multiple autism-risk genes [2]. These studies suggest that the memory system of the animal brain processes conflicting experiences through specific mechanisms. However, whether conflicting experiences activate specific early signals in the memory system is still unclear. To answer this question, suitable paradigms and possible candidates are required. In mice and Drosophila, reversal learning is an ideal experimental paradigm that has contributed to the understanding of both cognitive flexibility and the pathogenesis of related diseases including depression [3] and autism [2]. Immediateearly genes (IEGs) are possible candidates in the perception of different experiences and relaying signals to the memory system. First, IEGs are dominant molecules of the first wave of gene transcription induced by neuronal
Tingting Liu and Linghan Wang have contributed equally to this work.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12264-020-00566-8) contains supplementary material, which is available to authorized users. & Qian Li [email protected] 1
School of Life Sciences, Tsinghua University, Beijing 100084, China
activity and have been suggested to be the major molecular links between external stimuli and internal neuronal modification to affect learning and memory [4, 5]. Second, IEGs respond differently to different types of stimulation [6, 7]. Drosophila is an appropriate model in which to study behavioral flexibility using reversal learning [1, 2, 8], and to test prospective assumptions based on various genetic tools [9]. Five well-known IEGs (c-fos, Arc, Egr1, Npas4, and Nr4a1), which all have orthologs in Drosophila, have been studied in learning and memory [5] and used to develop activity-dependent tools [10]. Hr38 (Nr4a1 ortholog) is reported to be responsive to many kinds of non-learning stimuli [7, 11]. As a c-fos ortholog, kay is responsive to single and repeated olfactory learning [12, 13]. For the purpose of finding potential specific early signals of conflicting experiences, we focused on testing whether the other three well-known IEGs (Arc, Egr1, and Npas4) respond specifically to reversal learning in Drosophila. In one-session aversive olfactory learning [14], flies were sequentially exposed to two odors: 3-octa
