Anne Albrecht

Autophagy is a conserved lysosomal degradation pathway essential for maintaining neuronal proteostasis and synaptic function. Postmitotic neurons critically depend on autophagy to sustain long-term...

Acute disturbances of the light-dark cycle may lead to cognitive impairments associated with disturbances in hippocampal functions in humans and rodent models that are potentially governed by subcortical modulation. In this study, we applied a jet-lag-like model in mice by introducing a six-hour delay of the switch towards the light, inactive phase of mice following a contextual fear conditioning training. Phase delay (PD) resulted in a reduced fear memory expression in male but not female mice, associated with an activation of orexinergic neurons in the lateral hypothalamus (LH) as well as of cells in the supramammillary nucleus (SuM) and in the hilus of the dorsal hippocampal dentate gyrus (DG) in male mice, as assessed by immunolabelling for the activity marker c-Fos. Mimicking the overactivation of SuM and DG by chemogenetic stimulation before contextual fear memory retrieval replicated the PD-induced phenotype, suggesting a direct contribution of the SuM and the DG on modulating fear expression after PD. Further circuit analysis by c-Fos revealed a reciprocal interaction between the SuM and the DG. In addition, orexinergic neurons in the LH were activated by chemogenetic stimulation of the SuM. Together, our results reveal that an acute, jet-lag-like phase shift applied during late consolidation stages induced deficits in fear memory expression associated with an overactivation of the SuM-DG pathway and the orexinergic system. These findings may provide insights into the subcortical modulation of memory-relevant circuits, with relevance for acute light-dark rhythm disruptions prevalent in modern societies as well as for disorders associated with memory disturbances. Significance statement: Acute disturbances of the light-dark cycle, as experienced during jet lag or shift work, are increasingly common and can impair memory and cognitive function. Here, we identify a brain circuit underlying jet-lag-induced fear memory deficits that occurs selectively in male, but not female mice. A six-hour delay of the dark phase impaired recall of a previously learned fear memory in males, associated with overactivation of two interconnected brain regions, the supramammillary nucleus and the dentate gyrus of the hippocampus, as well as neurons producing the wake-promoting signal orexin. Artificially mimicking this overactivation was sufficient to reproduce the memory impairment, revealing a hypothalamo-hippocampal circuit that translates circadian disruption into memory deficits in male, with implications for cognitive disorders.

Immersive virtual reality learning environments (IVRLEs) are increasingly used in medical education, yet the role of environmental fidelity—particularly scene design—remains underexplored. This study examines how varying levels of fidelity and contextualization affect motivational and cognitive outcomes. Eighty-seven medical students were randomly assigned to one of three scene conditions: a minimalistic “Blank Scene,” a “Reconstructed Classroom Scene”, or an “Inside-Human Scene”. All students used a custom-developed application to learn about embryonic heart development. We measured virtual presence, intrinsic motivation, cognitive load, learning outcomes, and usability. Results showed that scene design influenced virtual presence, selected aspects of intrinsic motivation, cognitive load, and learning outcomes. The Inside-Human Scene elicited higher physical and self-presence as well as higher comprehension scores compared to the Reconstructed Classroom Scene. The Reconstructed Classroom Scene was associated with higher extraneous cognitive load. Intrinsic cognitive load was rated higher in the Inside-Human Scene, while germane cognitive load did not differ between conditions. No significant differences were found for task performance or factual recall. Overall, the findings indicate that scene design in IVRLEs affects how learners engage with complex content and may support deeper understanding when perceptual and contextual properties are coherent, while visually detailed environments may increase extraneous cognitive demands without improving learning.

Macroautophagy/autophagy, a critical cellular degradation pathway essential for maintaining neuronal proteostasis, declines with age and has been increasingly implicated in the regulation of synaptic integrity and circuit resilience. Neuropeptide Y (NPY), the most abundantly expressed neuropeptide in the mammalian brain, has emerged as a key modulator of both autophagy and aging-related processes. In Drosophila , the NPY-family peptide short Neuropeptide F (sNPF) has been shown to causally influence aging-associated changes in synaptic architecture and function, particularly at the presynaptic active zone (AZ), via non-cell autonomous mechanisms. Extending this concept to mammals, we investigated whether NPY and autophagy interact within NPY-secreting neurons to regulate age-related AZ remodeling. Our results indicate that hypothalamic NPY/AgRP neurons may exert geroprotective effects through the release of NPY and potentially other signaling molecules, thereby influencing both metabolic homeostasis and brain-wide synaptic function. These data suggest a conserved role for autophagy in maintaining presynaptic organization and resilience during aging.

Purpose: High-resolution multislice CT (HR-MSCT) and cone beam CT (CBCT) are commonly used for preoperative temporal bone imaging, with HR-MSCT often preferred due to its shorter scan duration and lower susceptibility to motion artifacts. However, recent advancements in accelerated flat panel CT (Acc-FPCT) available with the latest generation angiography systems have addressed traditional limitations of CBCT by significantly decreasing scan time. This cadaver-based study evaluates the diagnostic performance and radiation dose of Acc-FPCT compared to HR-MSCT in preoperative temporal bone imaging. Methods: Six different Acc-FPCT protocols were acquired on five whole-head cadaveric specimens (ten temporal bones). Three neuroradiologists experienced in temporal bone imaging assessed the image quality of Acc-FPCT protocols in comparison to that of HR-MSCT for the visualization of 31 landmarks of middle and inner ear using a 5-point Likert scale. We also compared radiation dose parameters (CT dose index and dose length product) among the protocols. Results: Two high-Resolution Acc-FPCT protocols were found to be superior to HR-MSCT by all raters (p < 0.001). There were no significant differences between the two HR-FPCT protocols (p = 0.25). The remaining Acc-FPCT protocols were rated significantly inferior to HR-MSCT. The inter-rater reliability was excellent (ICC (2,k) = 0.925; CI [0.92–0.93]). The dose length product was significantly lower in all Acc-FPCT protocols compared to HR-MSCT. Conclusion: The results of our cadaver-based study highlight the utility of certain Acc-FPCT protocols as a viable alternative to HR-MSCT in preoperative temporal bone imaging, improving the visualization of critical anatomical landmarks without increasing radiation exposure.

Orexins are wake-promoting neuropeptides that originate from hypothalamic neurons projecting to widespread brain areas throughout the central nervous system. They modulate various physiological functions via their orexin 1 (OXR1) and 2 (OXR2) receptors, including sleep-wake rhythm but also cognitive functions such as memory formation. Here, we provide a detailed analysis of OXR1 and OXR2 mRNA expression profiles in the dorsal hippocampus as a key region for memory formation, using RNAscope multiplex in situ hybridization. Interconnected subareas relevant for cognition and memory such as the medial prefrontal cortex and the nucleus reuniens of the thalamus were assessed as well. Both receptor types display distinct profiles, with the highest percentage of OXR1 mRNA-positive cells in the hilus of the dentate gyrus. Here, the content of OXR1 mRNA per cell was slightly modulated at selected time points over a 12 h light/ 12 dark light phase. Using RNAScope and quantitative polymerase chain reaction approaches, we began to address a cell-type specific expression of OXR1 in hilar GABAergic interneurons. The distinct expression profiles of both receptor subtypes within hippocampal subareas and circuits provide an interesting basis for future interventional studies on orexin receptor function in spatial and contextual memory.

Where traditional media and methods reach their limits in anatomy education, mixed-reality (MR) environments can provide effective learning support because of their high interactivity and spatial visualization capabilities. However, the underlying design and pedagogical requirements are as diverse as the technologies themselves. This paper examines the effectiveness of individual- and collaborative learning environments for anatomy education, using embryonic heart development as an example. Both applications deliver the same content using identical visualizations and hardware but differ in interactivity and pedagogical approach. The environments were evaluated in a user study with medical students (n = 90) during their examination phase, assessing usability, user experience, social interaction/co-presence, cognitive load, and personal preference. Additionally, we conducted a knowledge test before and after an MR learning session to determine educational effects compared to a conventional anatomy seminar. Results indicate that the individual learning environment was generally preferred. However, no significant difference in learning effectiveness could be shown between the conventional approach and the MR applications. This suggests that both can effectively complement traditional seminars despite their different natures. Our study contributes to understanding how different MR settings could be tailored for anatomical education.

Orexins are wake-promoting neuropeptides that originate from hypothalamic neurons projecting to widespread brain areas throughout the central nervous system. They modulate various physiological functions via their orexin 1 (OXR1) and 2 (OXR2) receptors, including sleep-wake rhythm but also cognitive functions such as memory formation. Here, we provide a detailed analysis of OXR1 and OXR2 mRNA expression profiles in the dorsal hippocampus as a key region for memory formation, using RNAscope® multiplex in situ hybridization. Interconnected subareas relevant for cognition and memory such as the medial prefrontal cortex and the nucleus reuniens of the thalamus were assessed as well. Both receptor types display distinct profiles, with the highest percentage of OXR1 mRNA-positive cells in the hilus of the dentate gyrus. Here, the content of OXR1 mRNA per cell was slightly modulated at selected time points over a 12h light/ 12 dark light phase. Using RNAScope® and quantitative polymerase chain reaction approaches, we began to address a cell-type specific expression of OXR1 in hilar GABAergic interneurons. The distinct expression profiles of both receptor subtypes within hippocampal subareas and circuits provide an interesting basis for future interventional studies on orexin receptor function in spatial and contextual memory.