Sleep Is Required for Odor Exposure to Consolidate Memory and Remodel Olfactory Synapses

Abstract

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.

Modulation by NPYR underlies experience-dependent, sexually dimorphic learning

“…The sensory information from AWC and AWB is passed on to a downstream interneuron AIY, which has been implicated as an information checkpoint that regulates memory retrieval 32,[36][37][38] as well as hermaphrodite training and forgetting states of PA14 aversive learning 26,31 . We observed a reduction in calcium activity after training at the soma of the AIY neuron in both sexes (Fig.…”

Astrocyte-like CEPsh glia respond to stress

“…Though the C. elegans' sensory ensheathing glia (AMsh) have been shown to detect odorants and drive olfactory adaptation (Duan et al, 2020), it remains unknown if their astrocytes respond directly or indirectly to environmental stimuli. Therefore, we asked whether the CEPsh cells are modulated during a spaced the olfactory training paradigm in which animals learn to avoid the innately attractive odorant, butanone by repeatedly pairing the odor with starvation and exercise (Chandra et al, 2022; Kauffamnn et al, 2011). The memory from this training remains for at least 24 hours (Chandra et al, 2022).…”

“…Therefore, we asked whether the CEPsh cells are modulated during a spaced the olfactory training paradigm in which animals learn to avoid the innately attractive odorant, butanone by repeatedly pairing the odor with starvation and exercise (Chandra et al, 2022; Kauffamnn et al, 2011). The memory from this training remains for at least 24 hours (Chandra et al, 2022). In particular, we asked whether the cephalic sheath (CEPsh) glia, the astrocyte equivalent in C. elegans, integrate information from outside the animal with the animal's internal, physiological, state.…”