Dopamine-mediated interactions between short- and long-term memory dynamics

• 成果类型: Article
• 署名作者: Huang, Cheng; Luo, Junjie; Woo, Seung Je; Roitman, Lucas A.; Li, Jizhou; Pieribone, Vincent A.; Kannan, Madhuvanthi; Vasan, Ganesh; Schnitzer, Mark J.
• 署名单位: Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University; Yale University; The John B Pierce Laboratory, Inc; Yale University; Stanford University; Washington University (WUSTL); Chinese University of Hong Kong; University of Minnesota System; University of Minnesota Twin Cities
• 刊物名称: Nature
• ISSN/ISSBN: 0028-3807
• DOI: 10.1038/s41586-024-07819-w
• 发表日期: 2024-10-31
• 页码: 1141-1149
• 关键词: drosophila; valence; neurotransmitter; amygdala; neurons; spikes; innate; flies; MODEL

摘要

In dynamic environments, animals make behavioural decisions on the basis of the innate valences of sensory cues and information learnt about these cues across multiple timescales(1-3). However, it remains unclear how the innate valence of a sensory stimulus affects the acquisition of learnt valence information and subsequent memory dynamics. Here we show that in the Drosophila brain, interconnected short- and long-term memory units of the mushroom body jointly regulate memory through dopamine signals that encode innate and learnt sensory valences. By performing time-lapse in vivo voltage-imaging studies of neural spiking in more than 500 flies undergoing olfactory associative conditioning, we found that protocerebral posterior lateral 1 dopamine neurons (PPL1-DANs)(4) heterogeneously and bidirectionally encode innate and learnt valences of punishment, reward and odour cues. During learning, these valence signals regulate memory storage and extinction in mushroom body output neurons (MBONs)(5). During initial conditioning bouts, PPL1-gamma 1pedc and PPL1-gamma 2 alpha ' 1 neurons control short-term memory formation, which weakens inhibitory feedback from MBON-gamma 1pedc>alpha/beta to PPL1-alpha ' 2 alpha 2 and PPL1-alpha 3. During further conditioning, this diminished feedback allows these two PPL1-DANs to encode the net innate plus learnt valence of the conditioned odour cue, which gates long-term memory formation. A computational model constrained by the fly connectome(6,7) and our spiking data explains how dopamine signals mediate the circuit interactions between short- and long-term memory traces, yielding predictions that our experiments confirmed. Overall, the mushroom body achieves flexible learning through the integration of innate and learnt valences in parallel learning units sharing feedback interconnections. This hybrid physiological-anatomical mechanism may be a general means by which dopamine regulates memory dynamics in other species and brain structures, including the vertebrate basal ganglia.