Sleep is required for odor exposure to consolidate memory and remodel olfactory synapses.

Sleep is conserved across phyla and is shown here to be required for memory consolidation in the nematode, C. elegans. However, it is unclear how sleep collaborates with experience to change specific neurons and associated synapses to ultimately affect behavior. C. elegans neurons have defined synaptic connections and described contributions to specific behaviors. We show that spaced odor-training induces long-term memory, which transits a labile period before being stably maintained. This post-training labile period is required for long-term memory. Memory consolidation, but not acquisition, requires a single interneuron, AIY, which plays a role in odor-seeking behavior. We find that sleep and conditioning mark inhibitory synaptic connections between the butanone-sensing AWC neuron and AIY to decrease synapses and it is in the post-sleep wake phase that memory-specific synaptic changes occur. Thus, we demonstrate in the living organism how sleep initiates events lasting beyond the period of sleep to drive memory consolidation.