摘要
Learned experiences are not necessarily consolidated into long-term memory (LTM) unless they are periodic and meaningful. LTM depends on de novo protein synthesis mediated by cyclic AMP response element-binding protein (CREB) activity. In Drosophila, two creb genes (crebA, crebB) and multiple CREB isoforms have reported influences on aversive olfactory LTM in response to multiple cycles of spaced conditioning. How CREB isoforms regulate LTM effector genes in various neural elements of the memory circuit is unclear, especially in the mushroom body (MB), a prominent associative center in the fly brain that has been shown to participate in LTM formation. Here, we report that i) spaced training induces crebB expression in MB α-lobe neurons and ii) elevating specific CREBB isoform levels in the early α/β subpopulation of MB neurons enhances LTM formation. By contrast, learning from weak training iii) induces 5-HT1A serotonin receptor synthesis, iv) activates 5-HT1A in early α/β neurons, and v) inhibits LTM formation. vi) LTM is enhanced when this inhibitory effect is relieved by down-regulating 5-HT1A or overexpressing CREBB. Our findings show that spaced training-induced CREBB antagonizes learning-induced 5-HT1A in early α/β MB neurons to modulate LTM consolidation. We thank the Bloomington Drosophila stock center, Vienna Drosophila RNAi Center and Kyoto Drosophila Genomics Resource Centers for fly stocks. We also thank the Developmental Studies Hybridoma Bank for the antibodies. We thank Chia–Ling Wu for preliminary cloning of the 5-HT1A promoter and Yuan-Ruei Huang for preliminary counting of the number of MB neurons. This work was supported by the Brain Research Center under the Higher Education Sprout Project cofunded by the Ministry of Education and the National Science and Technology Council in Taiwan, the Yushan Scholar Program from the Ministry of Education in Taiwan, and Dart NeuroScience LLC.