Fat cells have long-lasting (epigenetic) memory
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Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation
The hippocampus (HPC) has emerged as a critical player in the control of food intake, beyond its well-known role in memory. While previous studies have primarily associated the HPC with food intake inhibition, recent research suggests a role in appetitive processes. Here we identified spatially distinct neuronal populations within the dorsal HPC (dHPC) that respond to either fats or sugars, potent natural reinforcers that contribute to obesity development. Using activity-dependent genetic capture of nutrient-responsive dHPC neurons, we demonstrate a causal role of both populations in promoting nutrient-specific intake through different mechanisms. Sugar-responsive neurons encoded spatial memory for sugar location, whereas fat-responsive neurons selectively enhanced the preference and motivation for fat intake. Importantly, stimulation of either nutrient-responsive dHPC neurons increased food intake, while ablation differentially impacted obesogenic diet consumption and prevented diet-induced weight gain. Collectively, these findings uncover previously unknown orexigenic circuits underlying macronutrient-specific consumption and provide a foundation for developing potential obesity treatments.
A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan
Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms of how torpor affects aging, and whether hypothermic and hypometabolic states can be induced to slow aging and increase healthspan, remain unknown. Here we demonstrate that the activity of a spatially defined neuronal population in the preoptic area, which has previously been identified as a torpor-regulating brain region, is sufficient to induce a torpor-like state (TLS) in mice. Prolonged induction of TLS slows epigenetic aging across multiple tissues and improves healthspan. We isolate the effects of decreased metabolic rate, long-term caloric restriction, and decreased core body temperature (Tb) on blood epigenetic aging and find that the decelerating effect of TLSs on aging is mediated by decreased Tb. Taken together, our findings provide novel mechanistic insight into the decelerating effects of torpor and hibernation on aging and support the growing body of evidence that Tb is an important mediator of the aging processes.
Psychological booster shots targeting memory increase long-term resistance against misinformation
An increasing number of real-world interventions aim to preemptively protect or inoculate people against misinformation. Inoculation research has demonstrated positive effects on misinformation resilience when measured immediately after treatment via messages, games, or videos. However, very little is currently known about their long-term effectiveness and the mechanisms by which such treatment effects decay over time. We start by proposing three possible models on the mechanisms driving resistance to misinformation. We then report five pre-registered longitudinal experiments (Ntotal = 11,759) that investigate the effectiveness of psychological inoculation interventions over time as well as their underlying mechanisms. We find that text-based and video-based inoculation interventions can remain effective for one month—whereas game-based interventions appear to decay more rapidly—and that memory-enhancing booster interventions can enhance the diminishing effects of counter-misinformation interventions. Finally, we propose an integrated memory-motivation model, concluding that misinformation researchers would benefit from integrating knowledge from the cognitive science of memory to design better psychological interventions that can counter misinformation durably over time and at-scale.
Error-driven upregulation of memory representations
Learning an association does not always succeed on the first attempt. Previous studies associated increased error signals in posterior medial frontal cortex with improved memory formation. However, the neurophysiological mechanisms that facilitate post-error learning remain poorly understood. To address this gap, participants performed a feedback-based association learning task and a 1-back localizer task. Increased hemodynamic responses in posterior medial frontal cortex were found for internal and external origins of memory error evidence, and during post-error encoding success as quantified by subsequent recall of face-associated memories. A localizer-based machine learning model displayed a network of cognitive control regions, including posterior medial frontal and dorsolateral prefrontal cortices, whose activity was related to face-processing evidence in the fusiform face area. Representation strength was higher during failed recall and increased during encoding when subsequent recall succeeded. These data enhance our understanding of the neurophysiological mechanisms of adaptive learning by linking the need for learning with increased processing of the relevant stimulus category.
Trained immunity in type 2 immune responses
Immunological memory of innate immune cells, also termed “trained immunity”, allows for cross-protection against distinct pathogens, but may also drive chronic inflammation. Recent studies have shown that memory responses associated with type 2 immunity do not solely rely on adaptive immune cells, such as T- and B cells, but also involve the innate immune system and epithelial cells. Memory responses have been described for monocytes, macrophages and airway epithelial cells of asthmatic patients as well as for macrophages and group 2 innate lymphoid cells (ILC2) from allergen-sensitized or helminth-infected mice. The metabolic and epigenetic mechanisms that mediate allergen- or helminth-induced reprogramming of innate immune cells are only beginning to be uncovered. Trained immunity has been implicated in helminth-driven immune regulation and allergen-specific immunotherapy, suggesting its exploitation in future therapies. Here, we discuss recent advances and key remaining questions regarding the mechanisms and functions of trained type 2 immunity in infection and inflammation.
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