SleepCirc · Claustrum, Brainstem and Sleep: Mechanisms and Function

We will address fundamental questions about sleep mechanisms, function and evolution, and about the role of the claustrum, a forebrain area with hypothetical roles in attention and consciousness. These results are interesting in part because the claustrum has an ill-defined evolutionary origin and because its potential involvement in sleep has, to our knowledge, not been reported previously. This proposal exploits three new and previously unrelated results from the reptilian brain. (i) We discovered recently that, in the lizard Pogona vitticeps, slow-wave and REM sleep alternate in a clock-like fashion, suggesting the existence of regular sleep pattern generators in the brainstem. (ii) More recently, a single-cell RNA sequencing study of the reptilian brain by our laboratory, hinted that a small pallial area may be homologous to the mammalian claustrum. This homology acquired functional importance in a third, independent finding, based on electrophysiological recordings: (iii) sharp-wave ripples, a hallmark of Pogona slow-wave sleep, can be generated autonomously from an area that corresponds precisely to the transcriptomically-identified claustrum. This convergence provides a potential clue about claustrum function and evolution, especially because, in mammals at least, the claustrum is densely interconnected with the rest of the brain, especially cortex. Our neuroethological approach will exploit the unique advantages of Pogona sleep, combining scRNA-seq, tract-tracing, optogenetic, behavioral and electrophysiological approaches.