Howard Hughes Medical Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Chronobiology and Sleep Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
J Neurosci. 2022 May 4;42(18):3856-3867. doi: 10.1523/JNEUROSCI.0106-22.2022. Epub 2022 Mar 31.
Sleep is a universally conserved physiological state which contributes toward basic organismal functions, including cognitive operations such as learning and memory. Intriguingly, organisms can sometimes form memory even without sleep, such that display sleep-dependent and sleep-independent memory in an olfactory appetitive training paradigm. Sleep-dependent memory can be elicited by the perception of sweet taste, and we now show that a mixed-sex population of flies maintained on sorbitol, a tasteless but nutritive substance, do not require sleep for memory consolidation. Consistent with this, silencing sugar-sensing gustatory receptor neurons in fed flies triggers a switch to sleep-independent memory consolidation, whereas activating sugar-sensing gustatory receptor neurons results in the formation of sleep-dependent memory in starved flies. Sleep-dependent and sleep-independent memory relies on distinct subsets of reward signaling protocerebral anterior medial dopaminergic neurons (PAM DANs) such that PAM-β'2mp DANs mediate memory in fed flies whereas PAM-α1 DANs are required in starved flies. Correspondingly, we observed a feeding-dependent calcium increase in PAM-β'2mp DANs, but not in PAM-α1 DANs. Following training, the presence of sweet sugars recruits PAM-β'2mp DANs, whereas tasteless medium increases calcium in PAM-α1 DANs. Together, this work identifies mechanistic underpinnings of sleep-dependent memory consolidation, in particular demonstrating a role for the processing of sweet taste reward signals. Sleep is essential for encoding and consolidating memories, but animals must often suppress sleep for survival. Consequently, have evolved sleep-independent consolidation that allows retention of essential information without sleep. In the presence of food, sleep is required for memory, but mechanisms that transmit signals from food cues to regulate the need for sleep in memory are largely unknown. We found that sweet-sensing neurons drive the recruitment of specific reward signaling dopaminergic neurons to establish sleep-dependent memory. Conversely, in the absence of a sweet stimulus, different neurons are activated within the same dopaminergic cluster for sleep-independent memory consolidation. Therefore, the processing of sleep-dependent memory relies on the presence of sweet sugars that signal through reward circuitry.
睡眠是一种普遍存在的生理状态，有助于维持基本的机体功能，包括学习和记忆等认知活动。有趣的是，有些生物体在没有睡眠的情况下也能形成记忆，例如，在嗅觉性食物奖励训练范式中，果蝇表现出睡眠依赖性和睡眠非依赖性记忆。对甜味的感知可以诱发睡眠依赖性记忆，我们现在发现，在维持于无味但有营养的山梨糖醇上的雌雄混合群体中，记忆巩固不需要睡眠。与之一致的是，在进食的果蝇中沉默糖感觉味觉受体神经元会引发向睡眠非依赖性记忆巩固的转变，而激活糖感觉味觉受体神经元则会导致饥饿的果蝇形成睡眠依赖性记忆。睡眠依赖性和睡眠非依赖性记忆依赖于不同的奖赏信号中脑前内侧多巴胺能神经元（PAM DANs）亚群，例如，在进食的果蝇中，PAM-β'2mp DANs 介导记忆，而在饥饿的果蝇中需要 PAM-α1 DANs。相应地，我们观察到 PAM-β'2mp DANs 中存在与进食相关的钙增加，但 PAM-α1 DANs 中没有。在训练后，甜糖会募集 PAM-β'2mp DANs，而无味的中体会增加 PAM-α1 DANs 中的钙。总之，这项工作确定了睡眠依赖性记忆巩固的机制基础，特别是证明了甜味觉奖赏信号处理的作用。睡眠对于编码和巩固记忆至关重要，但动物为了生存经常不得不抑制睡眠。因此，动物已经进化出了睡眠非依赖性巩固机制，使得它们可以在不睡眠的情况下保留重要信息。在有食物的情况下，睡眠是记忆所必需的，但将食物线索传递的信号用于调节睡眠需求的机制在很大程度上尚不清楚。我们发现，甜觉神经元驱动特定的奖赏信号多巴胺能神经元的募集，以建立睡眠依赖性记忆。相反，在没有甜味刺激的情况下，相同多巴胺能簇内的不同神经元会被激活，用于睡眠非依赖性记忆巩固。因此，睡眠依赖性记忆的处理依赖于通过奖赏回路传递信号的甜味糖的存在。
