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Olfactory dysfunction precedes dementia in several neurodegenerative disorders such as Alzheimer’s disease (AD) or Parkinson’s Disease (PD), and AD/PD are associated with progressive sleep abnormalities. However, how sleep affects cognitive performance remains unclear, perhaps due to the complexities of the human nervous system. Here we demonstrate that the transparent model organism C. elegans which has well defined neural connection sleeps after repeated odor trainings. This provides us with a platform to dissect how sleep affects memory at a synaptic resolution. We identified that sleep after training is required for the animal to retain a long-term memory of the odor. We found that if animals do not sleep in the first two hours after training, memory is not consolidated. After identifying the neurons that are required for the memory, we show that the sensory-interneuron connections within the circuit are downscaled after sleep. Therefore, we found a time-specific requirement of sleep that modulates synaptic downscaling to preserve memory. Conversely, lack of sleep post-training erases the long-term memory and destabilizes the synaptic downscaling, indicating that modulating the amount of sleep is sufficient to modulate memory. These results make C. elegans an excellent tool to ask what molecular mechanisms, cell biological processes and circuit level reorganizations are engaged during sleep to promote memory. This understanding will provide insights into the functions of sleep that affects cognitive performance in neurodegenerative diseases.

SUMMARYAnimals with complex nervous systems demand sleep for memory consolidation and synaptic remodeling. Here we show that though theCaenorhabditis elegansnervous system has a limited number of neurons, sleep is necessary for both processes. In addition, it is unclear in any system if sleep collaborates with experience to alter synapses between specific neurons and whether this ultimately affects behavior.C. elegansneurons have defined connections and well-described contributions to behavior. We show that spaced odor-training and post-training sleep induce long-term memory. Memory consolidation, but not acquisition, requires a pair of interneurons, the AIYs, which play a role in odor-seeking behavior. In worms that consolidate memory, both sleep and odor conditioning are required to diminish inhibitory synaptic connections between the AWC chemosensory neurons and the AIYs. Thus, we demonstrate in a living organism that sleep is required for events immediately after training that drive memory consolidation and alter synaptic structures.