2 legs, 4 legs 🤷 6 legs - now we're talking!

Congrats!!

Just seeing this, looks terrific even to my currently jet-lagged brain, congrats Abhilasha!

Thanks, Caro! I see you’re going to be at CSHL next week. Will be there too, look fwd!

Thanks Mark! The mutants have been super helpful, thanks so much ! Re: axenic, yeah a student in Paul Shaw's lab at WashU had tried this experiment some years back when I was there, and didn't see anything for sleep then (in wild type flies).

More in the preprint – do check it out! Would love feedback. Didn’t think we would be doing classical neurogenetics tbh, but here we are! These genes are cool, lots to mine here (fini)

This expt I really like. We used @kayserlab.bsky.social’s sleep restriction protocol to enhance sleep behaviorally and saw improvements in memory! This comes straight from human psychology – cognitive behavioral therapy for insomnia (CBTI) amazing that it works in the fly! (12/n)

Finally, we asked if the memory defects of some AMP mutants could be reversed by enhancing sleep. We find that enhancing sleep of Bomanin mutants using the GABA agonist Gaboxadol robustly increased sleep and improved memory (11/n)

So these ‘immune effectors’ seem to act in glia to modulate sleep and memory. Indeed expression profiling suggests that glial might express many AMPs – cool! (10/n)

Group C are doubly mutant for the anti-fungal peptides Metchnikowin (mtk) and Drosomycin (Drs). We knocked down Mtk and Drs in different tissues and saw that glial knockdown mimicked the deletion mutants. (9/n).

The Group C mutants seem to be able to carry out (some) sleep functions sans much sleep. Very cool! But how do they do it? We first thought maybe the microbiome is messed up, so we eliminated the microbiome. And saw.. .. crickets (8/n)

Sleep in strongly associated with learning and memory. We find that most AMP mutants are impaired in learning and memory using @alexckeene.bsky.social’s gustatory assay. Counter-intuitively Group C mutants that sleep the least uniquely retained normal learning and memory (7/n)

We next evaluated sleep functions. As per the synaptic homeostasis hypothesis, extended waking upscales synapses. The Group C mutants that slept the least surprisingly showed lower synapse abundance (6/n)

Evaluating baseline sleep is ok, but sleep is also known to be plastic to environmental changes and ecological changes. We find that specific AMPs are required for context dep changes e.g. socialization and rocking induced sleep (5/n)

We next evaluated sleep homeostasis reasoning that low sleep might be a result of inability to generate needed sleep. Most mutants were unaffected, Group C mutants that sleep the least uniquely showed an exaggerated rebound. (4/n)

AMP mutants sleep less, with a longer latency i.e. they take longer to fall asleep. Sleep regulation by AMPs might be common (3/n)

Sleep and immunity are linked. But just how deeply is unclear. Here we obtained mutants in different antimicrobial peptides (AMPs), effectors of fly innate immunity, and characterized their roles in sleep and plasticity (2/n)