Clinical observations indicate that the paramedian region of the thalamus is a critical node for controlling wakefulness. However, the specific nucleus and neural circuitry for this function remain unknown. Using in vivo fiber photometry or multichannel electrophysiological recordings in mice, we found that glutamatergic neurons of the paraventricular thalamus (PVT) exhibited high activities during wakefulness. Suppression of PVT neuronal activity caused a reduction in wakefulness, whereas activation of PVT neurons induced a transition from sleep to wakefulness and an acceleration of emergence from general anesthesia. Moreover, our findings indicate that the PVT–nucleus accumbens projections and hypocretin neurons in the lateral hypothalamus to PVT glutamatergic neurons’ projections are the effector pathways for wakefulness control. These results demonstrate that the PVT is a key wakefulness-controlling nucleus in the thalamus.

Cognitive decline remains an unaddressed problem for the elderly. We show that myelination is highly active in young mice and greatly inhibited in aged mice, coinciding with spatial memory deficits. Inhibiting myelination by deletion of Olig2 in oligodendrocyte precursor cells impairs spatial memory in young mice, while enhancing myelination by deleting the muscarinic acetylcholine receptor 1 in oligodendrocyte precursor cells, or promoting oligodendroglial differentiation and myelination via clemastine treatment, rescues spatial memory decline during aging. Preventing age-related cognitive decline represents an unmet need for the elderly 1. Multiple lines of magnetic resonance imaging evidence have identified abnormalities in the white matter of aged human brains 2. Recent studies have revealed that myelin remodeling persists

Cognitive representation of the environment requires a stable hippocampal map but the mechanisms maintaining map representation are unknown. Because sharp wave-ripples (SPW-R) orchestrate both retrospective and prospective spatial information, we hypothesized that disrupting neuronal activity during SPW-Rs affects spatial representation. Mice learned daily a new set of three goal locations on a multi-well maze. We used closed-loop SPW-R detection at goal locations to trigger optogenetic silencing of a subset of CA1 pyramidal neurons. Control place cells (non-silenced or silenced outside SPW-Rs) largely maintained the location of their place fields after learning and showed increased spatial information content. In contrast, the place fields of SPW-R-silenced place cells remapped, and their spatial information remained unaltered. SPW-R silencing did not impact the firing rates or the proportions of place cells. These results suggest that interference with SPW-R-associated activity during learning prevents the stabilization and refinement of the hippocampal map.

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Background and Purpose-Our previous study demonstrated that pretreatment with electroacupuncture (EA) induces rapid tolerance to focal cerebral ischemia. The present study was aimed to investigate the involvement of the endocannabinoid system in the early neuroprotection conferred by EA pretreatment in the animal model of focal cerebral ischemia. Methods-Two hours after the end of EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 minutes in male Sprague-Dawley rats or male C57BL/6 mice. The neurobehavioral scores, infarction volumes, and neuronal apoptosis were evaluated at 24 hours or 7 days after reperfusion in the presence or absence of AM251 (a selective cannabinoid receptor type 1 [CB1] receptor antagonist) or CB1 short interfering RNA. The expression of CB1 receptor and the content of endocannabinoids in the brains were also investigated. Results-EA pretreatment reduced infarct size, improved neurological outcome, and inhibited neuronal apoptosis at 24 hours or 7 days after reperfusion. The beneficial effects were abolished by AM251. CB1 knockdown by CB1 short interfering RNA attenuated EA pretreatment-induced neuroprotection. EA pretreatment upregulated the neuronal expression of CB1 receptor in the rat brains and elevated the brain tissue content of the endocannabinoid 2-arachidonylglycerol and N-arach-idonoylethanolamine-anandamide. Pretreatment with 2-arachidonylglycerol and N-arach-idonoylethanolamine-anandamide also reduced infarct size and improved neurological outcome. Conclusion-We conclude that pretreatment with EA increases the production of endocannabinoid 2-arachidonylglycerol and N-arach-idonoylethanolamine-anandamide, which elicits protective effects against transient cerebral ischemia through CB1 receptors. These results suggest a novel mechanism of EA pretreatment-induced rapid tolerance to focal cerebral ischemia.