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Enhanced sleep improves learning and memory in flies with learning deficits

In their recent paper published in Sleep, scientists in the lab of Paul Shaw, PhD, professor of neuroscience at Washington University in St. Louis, probe how sleep can support episodic memory by testing spatial learning in Drosophila melanogaster. Krishna Melnattur, PhD, assistant professor at Ashoka University and a former staff scientist in the Shaw lab, and colleagues show that sleep induction is sufficient to rescue flies’ learning deficits caused by sleep deprivation, genetic mutations or natural aging.

Paul Shaw
Paul Shaw, PhD

“Collectively our results demonstrate a critical role for sleep in supporting Spatial Learning in flies,” the authors write in their publication.

These findings follow up on a 2015 study from the lab, published in Current Biology¸ that demonstrated for the first time a restorative effect of sleep for flies with learning deficits. This study suggested that sleep might have a generalized effect on learning, as it improved the flies’ performance on both short-term and long-term memory tasks that relied on different neurotransmitter systems. Their present study endeavors to determine the extent of this generalizability by challenging the flies in yet another context: episodic memory, the flies’ ability to remember experiences.

Melnattur and colleagues tested episodic memory in flies by adapting a spatial learning paradigm that is analogous to the Morris water maze, which is often used to test rodents’ ability to form and remember meaningful associations between visual cues and features of their physical environment. In this assay, the flies similarly must learn a series of visual cues to help them efficiently navigate a changing environment. The flies traverse an aversively warm environment until they locate the spot that has been cooled to an appetitive temperature. Flies that successfully learn the visual cues associated with the location of the cooled spot consistently and quickly get there, whereas flies that fail to learn the visual cues take significantly longer to perform the task. Typically, scientists perform this assay on groups of flies – which requires hours of video analysis – so Shaw’s group decided to abandon the “fancy software,” Shaw says, and instead take an old-school approach to monitoring behavior and “just watch” flies one-by-one as they went through the assay.

When Melnattur and colleagues either pharmacologically or genetically induced more total sleep time in these flies, they saw a dramatic reversal in outcome—the flies completed the task better than they had before—demonstrating that enhancing sleep remediates learning and memory deficits.

Shaw says that it was immediately evident to his colleagues that they could “actually watch the flies learn in real time.” Within minutes, the wildtype flies had learned the association between the visual cues and the location of the cooled spot, apparently orienting their bodies at the end of each behavioral trial to find the subsequent cue.

After extensively characterizing the spatial learning paradigm in two wildtype fly strains under normal sleep conditions, Melnattur and colleagues subjected the flies to a sleep deprivation protocol. They found that the sleep-deprived flies exhibited learning deficiencies and failed to form an association between visual cues and the location of the cooled spot. This finding confirmed that sleep was important for episodic memory in flies, as Shaw and colleagues had suspected, leading them to test whether sleep induction could rescue learning in models with learning and memory deficiencies.

Melnattur and colleagues repeated this assay in aged wildtype and rutabaga mutant flies, which have extensive learning deficits. As expected, when the flies experienced normal sleep, neither the aged nor mutant flies were able to perform the spatial learning assay as well as the control flies did. When Melnattur and colleagues either pharmacologically or genetically induced more total sleep time in these flies, they saw a dramatic reversal in outcome—the flies completed the task better than they had before—demonstrating that enhancing sleep remediates learning and memory deficits.

Shaw emphasized that they only observed the benefit of inducing extra sleep in flies that exhibited learning deficiencies, not in wildtype flies. He suggests that his lab’s results indicate that sleep functions as the ultimate “neuromodulator of the brain,” acting on mechanisms the brain has evolved to learn and carry out basic cognitive functions. When flies experience sleep deprivation or have mutations that prevent learning, they require additional sleep to restore the brain to its “default state.” Shaw says, “we can make these animals sleep – we can make them better.”