美国斯坦福大学Mark J. Schnitzer等研究人员合作揭示多巴胺介导的短期和长期记忆动态之间的相互作用。2024年7月22日,《自然》杂志在线发表了这项成果。
研究人员展示了果蝇大脑中蘑菇体的短期和长期记忆单元通过编码先天和学习到的感觉效价的多巴胺信号共同调节记忆。通过对超过500只果蝇进行嗅觉联想条件反射的实时体内电压成像研究,研究人员发现原大脑后侧1型多巴胺神经元(PPL1-DAN)以异质和双向的方式编码惩罚、奖励和气味线索的先天和学习效价。在学习过程中,这些效价信号调节蘑菇体输出神经元(MBON)中的记忆存储和消退。在初始条件反射训练中,PPL1-γ1pedc和PPL1-γ2α’1神经元控制短期记忆的形成,这削弱了MBON-γ1pedc>α/β对PPL1-α’2α2和PPL1-α3的抑制反馈。
在进一步的训练过程中,这种反馈的减弱使得这两个PPL1-DAN能够编码条件气味线索的净先天加学习效价,从而控制长期记忆的形成。一个由果蝇连通图和这些神经脉冲数据约束的计算模型解释了多巴胺信号如何介导短期和长期记忆痕迹之间的电路交互,并提出了研究人员实验所验证的预测。总体而言,蘑菇体通过在共享反馈互连的平行学习单元内整合先天和学习效价实现灵活学习。这种混合生理解剖机制可能是多巴胺调节记忆动态的一般方式,适用于其他物种和脑结构,包括脊椎动物的基底神经节。
研究人员表示,在动态环境中,动物根据感觉线索的先天效价和跨多个时间尺度学习到的关于这些线索的信息做出行为决策。然而,尚不清楚感觉刺激的先天效价如何影响学习到的效价信息的获取以及随后的记忆动态。
附:英文原文
Title: Dopamine-mediated interactions between short- and long-term memory dynamics
Author: Huang, Cheng, Luo, Junjie, Woo, Seung Je, Roitman, Lucas A., Li, Jizhou, Pieribone, Vincent A., Kannan, Madhuvanthi, Vasan, Ganesh, Schnitzer, Mark J.
Issue&Volume: 2024-07-22
Abstract: In dynamic environments, animals make behavioral decisions based on the innate valences of sensory cues and information learnt about these cues across multiple timescales1–3. However, it remains unclear how the innate valence of a sensory stimulus affects 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 via dopamine signals that encode innate and learnt sensory valences. Through time-lapse, in vivo voltage-imaging studies of neural spiking in >500 flies undergoing olfactory associative conditioning, we found that protocerebral posterior lateral 1 dopamine neurons (PPL1-DANs)4 heterogeneously and bi-directionally encode innate and learnt valences of punishment, reward, and odor cues. During learning, these valence signals regulate memory storage and extinction in mushroom body output neurons (MBONs)5. In initial conditioning bouts, PPL1-γ1pedc and PPL1-γ2α’1 neurons control short-term memory formation, which weakens inhibitory feedback from MBON-γ1pedc>α/β to PPL1-α’2α2 and PPL1-α3. During further conditioning, this diminished feedback allows these two PPL1-DANs to encode the net innate plus learnt valence of the conditioned odor cue, which gates long-term memory formation. A computational model constrained by the fly connectome6,7 and our spiking data explains how dopamine signals mediate the circuit interactions between short- and long-term memory traces, yielding predictions that our experiments confirm. Overall, the mushroom body achieves flexible learning via the integration of innate and learnt valences within parallel learning units sharing feedback interconnections. This hybrid physiologic-anatomic mechanism may be a general means by which dopamine regulates memory dynamics in other species and brain structures, including the vertebrate basal ganglia.
DOI: 10.1038/s41586-024-07819-w
Source: https://www.nature.com/articles/s41586-024-07819-w
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html