Brain Research Center, National Tsing Hua University, Hsinchu 30013, Taiwan.
Department of Psychological Sciences, University of San Diego, San Diego, CA 92110.
Proc Natl Acad Sci U S A. 2021 Sep 14;118(37). doi: 10.1073/pnas.2100624118.
Episodic events are frequently consolidated into labile memory but are not necessarily transferred to persistent long-term memory (LTM). Regulatory mechanisms leading to LTM formation are poorly understood, however, especially at the resolution of identified neurons. Here, we demonstrate enhanced LTM following aversive olfactory conditioning in when the transcription factor cyclic AMP response element binding protein A (CREBA) is induced in just two dorsal-anterior-lateral (DAL) neurons. Our experiments show that this process is regulated by protein-gene interactions in DAL neurons: (1) transcription is induced by training and repressed by overexpression, (2) CREBA bidirectionally modulates LTM formation, (3) overexpression enhances training-induced gene transcription, and (4) increasing membrane excitability enhances LTM formation and gene expression. These findings suggest that activity-dependent gene expression in DAL neurons during LTM formation is regulated by CREB proteins.
情景事件经常被整合到不稳定的记忆中，但不一定被转移到持久的长期记忆（LTM）中。然而，导致 LTM 形成的调节机制知之甚少，特别是在已识别神经元的分辨率方面。在这里，我们证明了在仅仅两个背侧-前外侧（DAL）神经元中诱导转录因子环磷酸腺苷反应元件结合蛋白 A（CREBA）后，厌恶嗅觉条件反射会增强 LTM。我们的实验表明，这个过程是由 DAL 神经元中的蛋白-基因相互作用调节的：（1）转录是由训练诱导的，而被 过表达抑制，（2）CREBA 双向调节 LTM 的形成，（3） 过表达增强训练诱导的基因转录，（4）增加膜兴奋性增强 LTM 的形成和基因表达。这些发现表明，在 LTM 形成过程中，DAL 神经元中的活性依赖性基因表达受 CREB 蛋白调节。
