Natsubori, A. | Search bioRxiv

bioRxiv2024

Immediate glucose signaling transmitted via the vagus nerve in gut-brain neural communication

Sucrose consumption is influenced by certain gut-brain signaling mechanisms. Among these, one pathway involves neuropod cells, which form synaptic connections with the vagus nerve, leading to the immediate activation of central dopaminergic pathways. This study explored the role of the frontal cortex in its process. We found that the vagus nerves immediate activation is mediated by the sodium-glucose cotransporter 1 (SGLT1) of neuropod cells after the intragastric glucose injection in mice. Also, we showed that the involvement of both astrocytes and neurons in the frontal cortex via D2 and D1 dopamine receptors, respectively, by in vivo Ca2+ imaging. Finally, we revealed that psychological stress, which induces a reduction in sucrose preference, significantly diminishes the activation levels of both the vagus nerve and the frontal cortex. These findings highlight the role of a comprehensive gut-brain network in modulating sucrose preference, involving neuropod cells, the vagus nerve, and the frontal cortex. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/586971v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1f28baeorg.highwire.dtl.DTLVardef@b053a9org.highwire.dtl.DTLVardef@449431org.highwire.dtl.DTLVardef@5d3ad9_HPS_FORMAT_FIGEXP M_FIG C_FIG

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bioRxiv2023

Dopamine receptor type 2-expressing medium spiny neurons in the ventral lateral striatum have a non-REM sleep-induce function

Dopamine receptor type 2-expressing medium spiny neurons (D2-MSNs) in the medial part of the ventral striatum (VS) induce non-REM (NREM) sleep from the wake state in animals. However, it is unclear whether D2-MSNs in the lateral part of the VS (VLS), which is anatomically and functionally different from the medial part of the VS, contribute to sleep-wake regulation. This study aims to clarify whether and how D2- MSNs in the VLS are involved in sleep-wake regulation. Our study found that specifically removing D2-MSNs in the VLS led to an increase in wakefulness time in mice during the dark phase using a diphtheria toxin-mediated cell ablation/dysfunction technique. D2-MSN ablation throughout the VS increased dark phase wakefulness time. These findings suggest that VLS D2-MSNs may induce sleep during the dark phase with the medial part of the VS. Next, our fiber photometric recordings revealed that the population intracellular calcium (Ca2+) signal in the VLS D2-MSNs increased during the transition from wake to NREM sleep. The mean Ca2+ signal level of VLS D2-MSNs was higher during NREM and REM sleep than during the wake state, supporting their sleep-inducing role. Finally, optogenetic activation of the VLS D2-MSNs during the wake state always induced NREM sleep, demonstrating the causality of VLS D2-MSNs activity with sleep-induction. Additionally, activation of the VLS D1-MSNs, counterparts of D2-MSNs, always induced wake from NREM sleep, indicating a wake- promoting role. In conclusion, VLS D2-MSNs could have an NREM sleep-inducing function in coordination with those in the medial VS. Significant statementThe sleep-inducing function of D2-MSNs in the medial part of the ventral striatum (VS) has been previously reported; however, their function in the lateral part of the VS (VLS) has not been elucidated. We demonstrated that the diphtheria toxin-induced ablation of D2-MSNs in the VLS, as well as in the entire VS, increased wakefulness time in mice during the dark phase. VLS D2-MSNs had higher average Ca2+ signals during NREM and REM sleep than wake state via fiber photometric recording. Furthermore, optogenetic activation of VLS D2-MSNs during wake state induced NREM sleep in mice. In conclusion, D2-MSNs in the VLS have an NREM sleep-inducing function in coordination with those in the medial VS.

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