Sleep has been robustly linked to hippocampal integrity and is considered important for cognitive function. However, it remains unclear how variations in sleep are associated with the structurally heterogeneous subfields of the hippocampus and how this association relates to cognition in healthy young adults. This study aimed to elucidate the multivariate relationships among sleep duration, quality, and timing, the specific hippocampal subfield volumes, and cognitive functions in a large sample of healthy young adults. We applied multiset canonical correlation analysis to data from 942 young adults (ages 22-37) from the Human Connectome Project. We examined relationships among self-reported sleep parameters (via the Pittsburgh Sleep Quality Index), high-resolution hippocampal subfield volumes, and a broad set of cognitive performance measures. We identified a single significant mode of covariation, wherein better sleep health-characterized by a moderate sleep duration (reflecting a nonlinear, inverted U-shaped relationship), higher sleep quality (e.g., fewer awakenings, less discomfort), and optimal sleep timing-was robustly associated with larger hippocampal volumes, particularly in the anterior subfields. This sleep-hippocampus pattern was also associated with enhanced cognitive performance. Our findings reveal a specific link among sleep, an anterior-dominant pattern of hippocampal structure, and cognition in healthy young adulthood. This suggests that the anterior hippocampus is a key anatomical structure involved in this association in healthy young adulthood.

Resurgence of sarin use in the Syrian conflict demonstrates that chemical weapons are a vivid threat. Like other organophosphate compounds, sarin inhibits acetylcholinesterase resulting in cholinergic crisis. The current antidote therapy includes atropine (a muscarinic cholinergic antagonist) + an oxime (e.g., pralidoxime) to reactivate the inhibited cholinesterases. Long-term sequelae reported in victims of the 1995 Tokyo subway sarin attack emphasize the need to improve neuroprotection and to delineate more precise biomarkers of intoxication severity. Previously, we proposed that brain oscillations could indicate exposure severity to a sublethal dose of a neurotoxic agent. In the present study, we evaluated the effects of atropine + pralidoxime in mice exposed to a sublethal dose of sarin (0.9 LD50) on changes in short-term recovery, brainwaves and behavioral patterns. We demonstrated the benefits of the antidotes on alleviation of the sarin-induced encephalopathy, stabilization of brain oscillations, and attenuation of anhedonia behavior. Nevertheless, mice exhibited work memory impairments associated with the disruption of theta oscillations during the task, the disruption of sleep architecture and the anxiety-like behavior when exposed to the non-convulsive sarin dose. These outcomes were not mitigated by atropine + pralidoxime administration. Our findings suggest that the currently recommended antidote for sarin poisoning provides only partial neuroprotection. Despite stabilizing brain waves in resting state, current antidote is not effective in preventing long-term neurobehavioral complications.

The neural representation of reward is underpinned by neurotransmitter systems; however, current human neuroimaging techniques cannot assess the receptor-specific contributions to reward processing. We investigated the relationships between reward-related neural representations and the expression patterns of 30 neurotransmitter receptor genes by combining meta-analytic functional neuroimaging maps with gene expression data from the Allen Human Brain Atlas. Clustering analysis revealed that serotonin receptor 2 A was co-expressed with other reward-related receptors, whereas the nociceptin (NOP) receptor exhibited a distinct expression pattern. Using elastic net regression with spatial null models, we observed that monetary reward maps showed significant positive spatial correlations with serotonin receptor 2 A expression and negative correlations with NOP receptor expression. Similar positive correlations with serotonin receptor 2 A were observed in the craving maps. Principal component regression provided complementary evidence, with both monetary reward and craving maps showing significant associations with components characterized by NOP receptor loadings. These findings from multiple analytical approaches suggest that reward processing involves both coordinated receptor networks and specialized receptor systems, particularly highlighting the opposing roles of the serotonin receptor 2 A and NOP systems. Our results provide insights into the molecular mechanisms underlying reward processing in the human brain, potentially informing targeted interventions for reward-related disorders.

Numerous mouse models of Alzheimer's disease (AD) have developed since the discovery of mutations causing familial AD. These models successfully recapitulate the progressive amyloid pathology over time, thus serving as indispensable tools for improving our understanding of the pathogenesis. However, there is a growing concern about artificial phenotypes in these transgenic mouse models, resulting from overexpression of mutant amyloid precursor protein (APP) under artificial promoters. To address this issue, App knock-in (KI) mice were developed to produce mutated human β-amyloid (Aβ) from the endogenous App locus. Since the first characterisation in 2014, gathering evidence has made significant progress in the phenotype analysis of this mouse model. Here, we provide an update on novel phenotypes observed in AppNL-G-F KI mice. In particular, we will highlight how the progression of amyloid pathology is related to neuronal pathology, behavioural phenotype, and microglial response.