Breaking free from the clocks tyranny restores memory to brain damaged flies

Dissel, S.; Morgan, E.; Cao, L.; Wakefield, Z. P.; Shetty, S.; Chan, D.; Duong, V.; Donlea, J. M.; Farah, H.; Loutrianakis, V.; Ford, M.; Streett, L.; Periandri, E.; Li, Z.; Huang, I.; Abdalla, D.; Kalra, A.; Sousani, L.; Holder, B.; McAdams, C.; van Swinderen, B.; Shaw, P. J.

doi:10.1101/2024.01.25.577231

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bioRxiv · 10.1101/2024.01.25.577231

Breaking free from the clocks tyranny restores memory to brain damaged flies

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Abstract

The relationship between sleep and memory is an active topic of investigation. In this context, we demonstrate that enhancing sleep restores memory to flies with ablated Mushroom Bodies (MB), a key memory center; this is consistent across several memory assays. Mapping the underlying circuitry reveals circadian modulation of a subset of Dopaminergic neurons (DANs) that modulate aversive learning. Using imaging, we show that MB-ablation disrupts, and sleep restores the time of day these neurons are most responsive. Knocking down the receptor for the clock output signal, Pigment-dispersing factor (Pdfr), in this subset of DANs restores memory to MB-ablated flies. Crucially, MB-ablation does not result in memory impairments in the absence of a functioning clock. Our results reveal neuromodulations key role in cognitive restoration, where sleep aids memory in damaged brains, but a functioning clock unexpectedly hinders this process.

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Dissel, S., Morgan, E., Cao, L., Wakefield, Z. P., Shetty, S., Chan, D., Duong, V., Donlea, J. M., Farah, H., Loutrianakis, V., Ford, M., Streett, L., Periandri, E., Li, Z., Huang, I., Abdalla, D., Kalra, A., Sousani, L., Holder, B., McAdams, C., van Swinderen, B., Shaw, P. J.. 2024-01-26. Breaking free from the clocks tyranny restores memory to brain damaged flies. https://doi.org/10.1101/2024.01.25.577231

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