The mammalian claustrum has ‘hub’-like connectivity and has been suggested to be crucial for higher cognition. Its evolutionary origins, however, remain unclear. By examining a brain area that generates sharp wave–ripples (SWRs) in sleeping Australian bearded dragons (Pogona vitticeps), Norimoto, Fenk et al. identify a reptilian claustrum, suggesting that it may be an evolutionarily ancient structure.
Pogona lizards exhibit short sleep cycles made up of alternating slow-wave sleep (SWS) and rapid eye movement (REM) sleep. The authors recorded SWRs in the dorsal ventricular ridge (DVR) of the pallium in Pogona lizard brains during SWS periods, as previously reported. Using multi-electrode arrays in DVR slices, the authors observed that SWRs propagated from the anterior medial DVR (amDVR) to the posterior lateral end of the DVR, indicating that SWRs might be generated in the amDVR.
The authors used single-cell RNA sequencing to detect 20 clusters of glutamatergic cells in the Pogona pallium. Clusters 19 and 20 expressed markers that mapped on to the SWR-generating amDVR. Some of the transcriptomic markers of clusters 19 and 20 are known markers of the mammalian claustrum, and a large fraction of the single-cell transcriptomes in these clusters resembled single-cell transcriptomes of the mouse claustrum. Thus, the amDVR is molecularly similar to the mammalian claustrum.
The amDVR was enriched for genes encoding receptors for dopamine, acetylcholine, serotonin and noradrenaline — neuromodulators that, in mammals, are involved in controlling sleep and wake states. The authors identified homologues of mammalian sleep-related nuclei in the Pogona diencephalon, midbrain and brainstem and, through retrograde and anterograde tracing, mapped their connectivity with the amDVR. This approach revealed that the amDVR receives inputs from many of these sleep-implicated areas, and projects to the Pogona homologues of the hippocampus and neocortex. Overall, these results suggest that the amDVR is the Pogona claustrum.
In an ex vivo Pogona forebrain preparation, injecting the amDVR with tetrodotoxin stopped SWR generation. Moreover, unilateral or bilateral amDVR lesions abolished SWRs on the ipsilateral side or both sides, respectively, but without altering the sleep cycle. Whereas treating the amDVR with dopamine increased SWR generation, treatment with acetylcholine or serotonin suppressed it. Thus, SWR production is sensitive to the neuromodulatory inputs to the amDVR.
“amDVR lesions abolished SWRs”
Last, the authors used transcriptomic data to look for a claustrum in turtles (Trachemys scripta). This pointed to a different area of anterior pallium that, in slices, also generated SWRs. The identification of putative claustra in these two distant reptiles suggests that the claustrum probably already existed in a common amniote ancestor of reptiles and mammals.
Norimoto, H. et al. A claustrum in reptiles and its role in slow-wave sleep. Nature 578, 413–418 (2020)