Consolidation of Sleep-Dependent Appetitive Memory Is Mediated by a Sweet-Sensing Circuit

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 Drosophila 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.SIGNIFICANCE STATEMENT Sleep is essential for encoding and consolidating memories, but animals must often suppress sleep for survival. Consequently, Drosophila 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.