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bioRxiv2025

Induction of cortical ON/OFF periods in awake mice fulfills sleep functions

Can animals obtain core benefits of sleep while remaining awake? In mammals, slow-wave sleep is characterized by synchronized neuronal activity alternating between ON and OFF periods. Slow-wave activity and synchrony reflect sleep need, are correlated with synaptic strength in cortical circuits, and promote synaptic down-selection and memory consolidation. To address the above question, we locally induced alternating ON/OFF periods during wakefulness using optogenetics in mice. This led to a local, ipsilateral reduction of slow-wave activity and synchrony during subsequent sleep and to reduced markers of synaptic strength. Moreover, bilateral induction of OFF periods over sensorimotor cortex during sleep deprivation restored memory consolidation. Thus, inducing ON/OFF activity during wakefulness is sufficient to reduce local sleep need and fulfills core functions of sleep.

neuroscience↗

bioRxiv2022

Synthetic torpor triggers a neuroprotective and regulated mechanism in the rat brain, leading to the reversibility of Tau protein hyperphosphorylation.

Hyperphosphorylated Tau protein (PPTau) is the hallmark of tauopathic neurodegeneration. During "synthetic torpor" (ST), a transient hypothermic state which can be induced in rats by the local pharmacological inhibition of the Raphe Pallidus, a reversible brain Tau hyperphosphorylation occurs. The aim of the present study was to elucidate the - as yet unknown - molecular mechanisms underlying this process, at both a cellular and systemic level. Different phosphorylated forms of Tau and the main cellular factors involved in Tau phospho-regulation were assessed by western blot in the parietal cortex and hippocampus of rats induced in ST, at either the hypothermic nadir or after the recovery of euthermia. Pro- and anti-apoptotic markers, as well as different systemic factors which are involved in natural torpor, were also assessed. Finally, the degree of microglia activation was determined through morphometry. Overall, the results show that ST triggers a regulated biochemical process which can counteract PPTau formation starting, unexpectedly even for a non-hibernator, from the hypothermic nadir. In particular, at the nadir, the glycogen synthase kinase-{beta} was largely inhibited in both regions, the antiapoptotic factor AKT was significantly activated in the hippocampus, and melatonin plasma levels were significantly increased, while a transient neuroinflammation was observed during the recovery period. Together, the present data suggest that ST can trigger a previously undescribed latent and regulated physiological process, that is able to cope with brain PPTau formation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/485745v3_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@12e4ccdorg.highwire.dtl.DTLVardef@b44201org.highwire.dtl.DTLVardef@598a7corg.highwire.dtl.DTLVardef@92df61_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗