Biology subjects

Albrecht, A.

Publications and source records attributed to Albrecht, A..

11 recordsLinked to original sources

bioRxiv2026

Subcortical-hippocampal circuits for mediating impaired contextual fear memory after an acute shift of the light/dark phase

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, associated with a sex-specific 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), 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 statementAcute 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, with implications for cognitive disorders and sex-specific vulnerability.

animal behavior and cognition↗

bioRxiv2026

Development and Validation of Thalia: A High-ResolutionPediatric Computational Model of a 10-Month-Old Infant

Numerical human models are essential to advance medical device design, safety assessment, and study how anatomical development influences physiological processes. Despite increasing availability of pediatric models, a critical gap remains in high-resolution, non-morphed whole-body models representing children around one year of age. Existing pediatric models are often derived from morphing older anatomies or lack sufficient tissue segmentation to accurately capture early developmental anatomy. This study introduces Thalia, a non-morphed, high-resolution numerical model of a healthy 10-month-old female. The model was constructed by segmenting 442 tissues from Magnetic Resonance Imaging data. Brain tissues were automatically segmented using an infant-specific FreeSurfer framework, followed by semi-automated and manual refinement in 3DSlicer. The model was validated by expert review and quantitative comparison with age-matched anatomical values reported in the literature. The resulting whole-body model provides detailed anatomical representation across the brain, musculoskeletal system, vasculature, and internal organs, enabling realistic assignment of tissue-specific properties for computational studies. It provides a versatile platform for pediatric medical device development, dosimetry, safety assessment, and bioelectromagnetic simulations. This pediatric numerical anatomical model is openly available as an open-source resource. HighlightsO_LIHigh-resolution model of a 10-month-old child developed from MRI data C_LIO_LI442 tissues segmented to capture early anatomical development accurately C_LIO_LIModel validated against expert review and age-matched anatomical data C_LIO_LIIllustrative Example of a pediatric transcranial magnetic stimulation use case C_LI

bioengineering↗

bioRxiv2025

Non-cell autonomous control of presynaptic remodeling by the hypothalamic autophagy/NPY axis

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.

neuroscience↗

bioRxiv2025

Neuronal networks in the dorsal hippocampus causally regulate rescue behavior in mice

Prosocial behaviors, such as rescuing individuals in need, are crucial for social cohesion across species. While key brain regions involved in rescue behavior have been identified, the underlying neural mechanisms remain unclear. The hippocampus (HPC), known for its role in memory and spatial navigation, also contributes to emotional and social processing. However, its specific involvement in prosocial behavior is not well understood. Here, we investigate the causal role of the HPC in learning and executing rescue behavior in mice. Using chemogenetics, we show that the dorsal HPC (dHPC), but not the ventral HPC (vHPC), is essential for acquiring rescue behavior. Calcium imaging of the dHPC reveals network consolidation during successful rescues, with distinct synchronized ensembles and activity patterns linked to liberations of an individual in need. These findings establish a novel role for the dHPC in prosocial behavior, providing insights into the neural mechanisms underlying empathy-driven actions.

neuroscience↗

bioRxiv2024

Current Reporting Practices in Human Neuroscience Research

Concerns for the replicability, reliability, and generalizability of human neuroimaging research have led to intense debates over sample size and open science practices, with more recent attention on the contributions of sampling and recruitment practices. Key to understanding the state of neuroscience research is an assessment of reporting practices that influence replicability, reliability, and generalizability. In this structured review, we evaluated reporting practice across three domains: (1) demographic (e.g., reporting participant race-ethnicity, age, any measure of socioeconomic position), (2) methodological (e.g., reporting recruitment methods, inclusion and exclusion criteria, why participants were excluded from analyses), and (3) open science and generalizability (e.g., analyses were preregistered, target population was stated). Included were 919 published MRI and fMRI studies from 2019 in nine top-ranked journals (N = 3,856 records screened). Reporting across domains was infrequent, with participant racial or ethnic identity (14.8%), reasons for missing imaging data (31.2%), and identification of a target population (19.4%) being particularly low/underreported. Reporting likelihood varied by study characteristics (e.g., participant age group) and was correlated across domains. The median sample size of studies was 55 participants. Study sample size, reporting frequency, was positively associated with two-year citation counts, providing some evidence that the complete reporting of demographic characteristics, methodological decisions, and open science and generalizability practices may not be as valued as study sample size. Recommendations for structural interventions at the journal level are proposed.

neuroscience↗

bioRxiv2024

Spatial mRNA expression patterns of orexin receptors in the dorsal hippocampus

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(R) 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(R) 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.

neuroscience↗

bioRxiv2023

Sex differences in anxiety and threat avoidance in GAD65 knock-out mice

Anxiety disorders have been linked to a disbalance of excitation and inhibition in a network of brain structures comprising frontal cortical regions, the amygdala and the hippocampus, among others. Recent imaging studies suggest sex differences in the activation of this anxiety network during the processing of emotional information. Rodent models with genetically altered {Upsilon}-amino butyric acid (GABA) neurotransmission allow studying the neuronal basis of such activation shifts and their relation to anxiety endophenotypes, but to date sex effects have rarely been addressed. Using mice with a null mutation of the GABA synthetizing enzyme glutamate decarboxylase 65 (GAD65-/-), we started to compare anxiety-like behavior and avoidance in male vs. female GAD65-/- mice and their wildtype littermates. In an open field, female GAD65-/- mice displayed increased activity, while male GAD65-/- mice showed an increased adaptation of anxiety-like behavior over time. GAD65-/- mice of both sexes had a higher preference for social interaction partners, which was further heightened in male mice. In male mice higher escape responses were observed during an active avoidance task. Together, female mice showed more stable emotional responses despite GAD65 deficiency. To gain insights into interneuron function in network structures controlling anxiety and threat perception, fast oscillations (10-45 Hz) were measured in ex vivo slice preparations of the anterior cingulate cortex (ACC). GAD65-/- mice of both sexes displayed increased gamma power in the ACC and a higher density of PV-positive interneurons, which are crucial for generating such rhythmic activity. In addition, GAD65-/- mice had lower numbers of somatostatin-positive interneurons in the basolateral amygdala and in the dorsal dentate gyrus especially in male mice, two key regions important for anxiety and active avoidance responses. Our data suggest sex differences in the configuration of GABAergic interneurons in a cortico-amygdala-hippocampal network controlling network activity patterns, anxiety and threat avoidance behavior. HighlightsO_LIRole of GABA in sex-specific anxiety endophenotypes demonstrated in GAD65-/- mice C_LIO_LISex- and GAD65-dependent alterations in anxiety, social preference and avoidance C_LIO_LIEnhanced in vitro gamma-beta oscillations in ACC slices of GAD65-/- mice C_LIO_LIIncreased parvalbumin(+) interneuron counts in ACC slices of GAD65-/- mice C_LIO_LIReduced somatostatin(+) interneuron counts in dorsal DG and BLA of male GAD65-/- mice C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/532980v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@85ac09org.highwire.dtl.DTLVardef@1e1a70aorg.highwire.dtl.DTLVardef@19dbbeforg.highwire.dtl.DTLVardef@9d52ff_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Choosing memory retrieval strategies: a critical role for inhibition in the dentate gyrus

Remembering the location of food is essential for survival. Rodents and humans employ mainly hippocampus-dependent spatial strategies, but when being stressed they shift to striatum-mediated stimulus-based strategies. To investigate underlying brain circuits, we tested mice with a heightened stress susceptibility due to a lack of the GABA-synthetizing enzyme GAD65 (GAD65-/- mice) in a dual solution task. Here, GAD65-/- mice preferred to locate a food reward in an open field via a proximal cue, while their wildtype littermates preferred a spatial strategy. The analysis of cFos co-activation across brain regions and of stress-induced mRNA expression changes of GAD65 pointed towards the hippocampal dorsal dentate gyrus (dDG) as a central structure for mediating stress effects on strategy choices via GAD65. Reducing the GAD65 expression locally in the dDG by a shRNA mediated knock down was sufficient to replicate the phenotype of the global GAD65 knock out and to increase dDG excitability. Using DREADD vectors to specifically interfere with dDG circuit activity during dual solution retrieval but not learning confirmed that the dDG modulates strategy choices and that a balanced excitability of this structure is necessary to establish spatial strategy preference. These data highlight the dDG as a critical hub for choosing between spatial and non-spatial foraging strategies.

neuroscience↗

bioRxiv2020

Split-HaloTag Imaging Assay for in vivo 3D-Microscopy and Subdiffractional Analyses of Protein-Protein Interactions

An ever-increasing number of intracellular multi-protein networks have been identified in plant cells. Split-GFP based protein-protein interaction assays combine the advantages of in vivo interaction studies in a native environment with additional visualisation of protein complex localisation. Due to its simple protocols, it has become one of the most frequently used methods. However, standard fluorescent proteins entail several drawbacks for sophisticated microscopy. With the HaloTag(R) system, these drawbacks can be overcome as this reporter forms covalent irreversible bonds with synthetic photostable fluorescent ligands. Dyes can be used in adjustable concentrations and are suitable for advanced microscopy methods. Therefore, we established the Split-HaloTag(R) imaging assay in plants which is based on the reconstitution of a functional HaloTag(R) protein upon protein-protein interaction and subsequent covalent binding of an added fluorescent ligand. Its suitability and robustness were demonstrated using well-characterised interactions as an example for protein-protein interaction at cellular structures: the molybdenum cofactor biosynthesis complex anchoring to filamentous actin. Additionally, a specific interaction was visualised with subdiffractional polarisation microscopy in a more distinctive manner as example for sophisticated imaging. Split-GFP and Split-HaloTag(R) can complement one another as Split-HaloTag(R) represents an alternative option and an addition to the large toolbox of in vivo methods. Therefore, this promising new Split-HaloTag(R) imaging assay provides a unique and sensitive approach for more detailed characterization of protein-protein interaction with specific microscopic techniques such as 3D-imaging, single molecule tracking and super-resolution microscopy.

plant biology↗

bioRxiv2020

A device for exploring the full angular excitation space - Can more angular projections improve determination of a molecules 3D-orientation in the presence of noise?

In the past, different methods have been presented to determine the 3D orientation of single molecules in a microscopic set-up by excitation polarization modulation. Using linearly polarized illumination from different directions and thereby measuring different 2D projections enables reconstructing the full 3D orientation. Theoretically, two projections suffice for a full 3D orientation determination if the intensities are properly calibrated. If they are not, a third projection will enable unambiguous orientation measurements. The question arises if three projections already contain the maximum information on the 3D orientation when also considering the limited number of available photons and shot noise in an experiment, or if detecting more projections or even continuously changing the projection direction during a measurement provides more information with an identical number of available photons. To answer this principle question, we constructed a simple device allowing for exploring any projection direction available with a particular microscope objective and tested several different excitation modulation schemes using simulated as well as experimental single molecule data. We found that three different projections in fact already do provide the maximum information also for noisy data. Our results do not indicate a significant improvement in angular precision in comparison to three projections, both when increasing the number of projections and when modulating the projection direction and polarization simultaneously during the measurement. In fluorescence microscopy polarized illumination from different directions enables the determination of the 3D orientation of single molecules by combining the 2D information of different projection directions. Ambiguities that emerge when using only two projections can be eliminated using a third projection. In a systematic study we show that - also considering the limited number of available photons and shot noise in an experiment - three projection directions already contain the maximum information on the 3D orientation. Our results do not indicate a significant improvement in angular precision in comparison to three projections, both when increasing the number of projections and when modulating the projection direction and polarization simultaneously during the measurement.

biophysics↗

bioRxiv2020

Amplitude Analysis of Polarization Modulation Data and 3D-Polarization Demodulation (3D-SPoD)

Super-resolution optical fluctuation imaging (SOFI) is a technique that uses the amplitude of fluorescence correlation data for improved resolution of fluorescence images. Here, we explore if also the amplitude of superresolution by polarisation demodulation (SPoD) data can be used to gain additional information about the underlying structures. Highly organized experimental as well a simulated actin filament data demonstrate a principle information gain from this approach. In addition, we explored theoretically the benefits of analyzing the entire 3D-polarization information instead of only 2D-projections thereof. Due to fundamental principles, the probability of finding parallel orientations is approaching zero in 3D-SPoD in contrast to 2D-approaches. Using the modulation-amplitude based analysis we explored systematically simulated 3D-single molecules data (for which the true structures are known) under different conditions that are typically observed in experiments. We found that this approach can significantly improve the distinction, reconstruction and localization. In addition, these approaches are less sensitive to uncertainties in the knowledge about the true experimental point-spread-function (PSF) used for reconstruction compared to approaches using non-modulated data. Finally, they can effectively remove higher levels of non-modulated back-ground intensity.

biophysics↗