Biology subjects

Schneider, A. M.

Publications and source records attributed to Schneider, A. M..

10 recordsLinked to original sources

bioRxiv2026

Environmental complexity reveals memory-guided search as the locus of learning in prey capture

Ethological behavior requires the integration of perception, memory, and decision-making, yet standard laboratory tasks are often too simplified to recruit these processes jointly. Here, mice that were expert hunters in a bare arena were challenged to capture live insect prey among objects that occlude vision and afford opportunities to hide. This revealed an axis of learning absent in an empty arena: mice improved not by refining pursuit but by reorganizing how they searched for concealed prey. An agent-based model showed that short-term memory and learning of object-specific values are sufficient to account for the behavior demonstrated by mice. A compact ethogram of object-directed actions revealed that animals selectively acquired the interactions most likely to expose prey. These results show that environmental complexity recruits memory- and value-guided search strategies. Reproducible with inexpensive materials, the paradigm and its open-source analyses offer a sensitive read-out of cognitive processes largely unobservable in conventional assays.

neuroscience↗

bioRxiv2025

Studying macromolecular composition in cell-cell interfaces using 3D membrane reconstitution systems

During direct communication between two cells, the plasma membranes of each cell serve as a platform for ligand-receptor interaction initiating downstream signalling cascades. In immune cell signalling, this cell-cell interface - the immune synapse - is highly spatiotemporally organized. Multiple stimulatory and co-stimulatory signals need to be integrated over time to ensure proper immune cell function. This process is still not fully understood given the vast complexity of interactions between proteins, lipids, glycocalyx and associated cortical actin cytoskeleton. To examine the impact of a single component, the use of model membrane systems has increased. Here, we developed a fully artificial system to study the interface between two vesicles and a semi-artificial one between a live cell and a vesicle to reconstitute 3D contacts. We investigated the distribution and reorganization of immune cell proteins at artificial and semi-artificial contacts. Using our vesicle-vesicle system, we show the enrichment and depletion of different proteins in the synapse. Using the cell-vesicle system we showed how different peptides with varying affinity presented by the same MHC class I affect T cell activation. We further explored the distribution of glycocalyx elements at the cell-cell contact and showed differential partitioning of different sugar moieties in the interface. While we focused on the T cell interface here, our model systems are powerful tools to study distribution and reorganization of lipids, proteins and glycocalyx components at any cell-cell contact.

biophysics↗

bioRxiv2024

A conserved code for anatomy: Neurons throughout the brain embed robust signatures of their anatomical location into spike trains.

Neurons in the brain are known to encode diverse information through their spiking activity, primarily reflecting external stimuli and internal states. However, whether individual neurons also embed information about their own anatomical location within their spike patterns remains largely unexplored. Here, we show that machine learning models can predict a neurons anatomical location across multiple brain regions and structures based solely on its spiking activity. Analyzing high-density recordings from thousands of neurons in awake, behaving mice, we demonstrate that anatomical location can be reliably decoded from neuronal activity across various stimulus conditions, including drifting gratings, naturalistic movies, and spontaneous activity. Crucially, anatomical signatures generalize across animals and even across different research laboratories, suggesting a fundamental principle of neural organization. Examination of trained classifiers reveals that anatomical information is enriched in specific interspike intervals as well as responses to stimuli. Within the visual isocortex, anatomical embedding is robust at the level of layers and primary versus secondary but does not robustly separate individual secondary structures. In contrast, structures within the hippocampus and thalamus are robustly separable based on their spike patterns. Our findings reveal a generalizable dimension of the neural code, where anatomical information is multiplexed with the encoding of external stimuli and internal states. This discovery provides new insights into the relationship between brain structure and function, with broad implications for neurodevelopment, multimodal integration, and the interpretation of large-scale neuronal recordings. Computational approximations of anatomy have potential to support in-vivo electrode localization.

neuroscience↗

bioRxiv2024

Rapamycin Treatment Reduces Brain Pericyte Constriction in Ischemic Stroke

The contraction and subsequent death of brain pericytes may play a role in microvascular no-reflow following the re-opening of an occluded artery during ischemic stroke. Mammalian target of rapamycin (mTOR) inhibition has been shown to reduce motility/contractility of various cancer cell lines and reduce neuronal cell death in stroke. However, the effects of mTOR inhibition on brain pericyte contraction and death during ischemia have not yet been investigated. Cultured pericytes exposed to simulated ischemia for 12 hours in vitro contracted after less than 1 h, which was about 7h prior to cell death. Rapamycin significantly reduced the rate of pericyte contraction during ischemia, however, it did not have a significant effect on pericyte viability at any time point. Rapamycin appeared to reduce pericyte contraction through a RhoA-dependent pathway, independent of changes in intracellular calcium. Using a mouse model of middle cerebral artery occlusion, rapamycin significantly increased the diameter of capillaries underneath pericytes and increased the number of open capillaries 30 minutes following recanalization. Our findings suggest rapamycin may be a useful adjuvant therapeutic to reduce pericyte contraction and improve cerebral reperfusion post-stroke.

neuroscience↗

bioRxiv2023

Post-stroke rapamycin treatment improves post-recanalization cerebral blood flow and outcome in rats

Ischaemic stroke treatment is limited to recanalizing the occluded vessel, while there is no approved adjunctive cerebroprotective therapy to protect either the neurons and parenchyma or the neurovascular unit. Pharmacological inhibition of mammalian target of rapamycin-1 (mTORC1) with rapamycin has shown promise in reducing infarct volume and improving functional outcomes. However, previous studies that investigated the effects of rapamycin on the vasculature and cerebral blood flow (CBF), administered rapamycin prior to or during stroke induction, thus limiting the potential for clinical translation. Therefore we investigated whether rapamycin maintains its cerebrovascular protective effect when administered immediately after recanalization following 90 minutes stroke in Wistar rats. We show, that rapamycin significantly improved post-recanalization cerebral blood flow (CBF), suggesting a beneficial neurovascular effect of rapamycin. Rats treated with rapamycin had smaller infarct volumes and improved functional outcomes compared to the control animals at three days post-stroke. The mechanisms of the overall positive effects seen in this study are likely due to rapamycins hyperacute effects on the neurovasculature, as shown with increased CBF during this phase. This paper shows that rapamycin treatment is a promising adjunct cerebroprotective therapy option for ischemic stroke.

neuroscience↗

bioRxiv2023

A non-oscillatory, millisecond-scale embedding of brain state provides insight into behavior.

Sleep and wake are understood to be slow, long-lasting processes that span the entire brain. Brain states correlate with many neurophysiological changes, yet the most robust and reliable signature of state is enriched in rhythms between 0.1 and 20 Hz. The possibility that the fundamental unit of brain state could be a reliable structure at the scale of milliseconds and microns has not been addressed due to the physical limits associated with oscillation-based definitions. Here, by analyzing high resolution neural activity recorded in 10 anatomically and functionally diverse regions of the murine brain over 24 h, we reveal a mechanistically distinct embedding of state in the brain. Sleep and wake states can be accurately classified from on the order of 100 to 101 ms of neuronal activity sampled from 100 m of brain tissue. In contrast to canonical rhythms, this embedding persists above 1,000 Hz. This high frequency embedding is robust to substates and rapid events such as sharp wave ripples and cortical ON/OFF states. To ascertain whether such fast and local structure is meaningful, we leveraged our observation that individual circuits intermittently switch states independently of the rest of the brain. Brief state discontinuities in subsets of circuits correspond with brief behavioral discontinuities during both sleep and wake. Our results suggest that the fundamental unit of state in the brain is consistent with the spatial and temporal scale of neuronal computation, and that this resolution can contribute to an understanding of cognition and behavior.

neuroscience↗

bioRxiv2023

Expression pattern of nicotinic acetylcholine receptor subunit transcripts in neurons and astrocytes in the ventral tegmental area and locus coeruleus

Acetylcholine is the endogenous agonist for the neuronal nicotinic acetylcholine receptor (nAChR) system, which is involved in attention, memory, affective behaviors, and substance use disorders. Brain nAChRs are highly diverse with 11 different subunits that can form multiple receptor subtypes, each with distinct receptor and pharmacological properties. Different neuronal cell types can also express different nAChR subtypes, resulting in highly complex cholinergic signaling. Identifying which nAChR subunit transcripts are expressed in cell types can provide an indication of which nAChR combinations are possible and which receptor subtypes may be most pharmacologically relevant to target. In addition to differences in expression across cell types, nAChRs also undergo changes in expression levels from adolescence to adulthood. In this study, we used fluorescent in situ hybridization to identify and quantify the expression of 4, 5, 6, {beta}2 and {beta}3 nAChR subunit transcripts in dopaminergic, GABAergic, glutamatergic, and noradrenergic neurons and astrocytes in the ventral tegmental area (VTA) and locus coeruleus (LC) in adult and adolescent, male and female C57BL/6J mice. There were distinct differences in the pattern of nAChR subunit transcript expression between the two brain regions. LC noradrenergic neurons had high prevalence of 6, {beta}2 and {beta}3 expression, with very low expression of 4, suggesting the 6(non-4){beta}2{beta}3 receptor as a main subtype in these neurons. VTA astrocytes from adult mice showed greater prevalence of 5, 6, {beta}2 and {beta}3 transcript compared with adolescent mice. These data highlight the complex nAChR expression patterns across brain region and cell type.

neuroscience↗

bioRxiv2022

The effects of fasting on ischemic infarcts in the rat

BackgroundInflammation has been found to be largely detrimental early in the acute phase of stroke but beneficial at more chronic stages. Fasting has been shown to reduce inflammation acutely. We aimed to determine whether post-ischemic fasting improves stroke outcomes through attenuated inflammation. MethodsAfter an endothelin-1 lesion was created in the striatum, animals were subjected to either normal feeding or water-only fasting for 24 hours. ResultsIt was found that at 24 hours, fasting reduced infarct volume and BBB breakdown and lowered both circulating and brain neutrophils. ConclusionsThese findings suggest that fasting is a potentially beneficial non-pharmacological additive therapeutic option for cerebral ischemia, which might act by reducing inflammation in the acute disease stage.

neuroscience↗

bioRxiv2020

Plasma proteomics reveals tissue-specific cell death and mediators of cell-cell interactions in severe COVID-19 patients

COVID-19 has caused over 1 million deaths globally, yet the cellular mechanisms underlying severe disease remain poorly understood. By analyzing several thousand plasma proteins in 306 COVID-19 patients and 78 symptomatic controls over serial timepoints using two complementary approaches, we uncover COVID-19 host immune and non-immune proteins not previously linked to this disease. Integration of plasma proteomics with nine published scRNAseq datasets shows that SARS-CoV-2 infection upregulates monocyte/macrophage, plasmablast, and T cell effector proteins. By comparing patients who died to severely ill patients who survived, we identify dynamic immunomodulatory and tissue-associated proteins associated with survival, providing insights into which host responses are beneficial and which are detrimental to survival. We identify intracellular death signatures from specific tissues and cell types, and by associating these with angiotensin converting enzyme 2 (ACE2) expression, we map tissue damage associated with severe disease and propose which damage results from direct viral infection rather than from indirect effects of illness. We find that disease severity in lung tissue is driven by myeloid cell phenotypes and cell-cell interactions with lung epithelial cells and T cells. Based on these results, we propose a model of immune and epithelial cell interactions that drive cell-type specific and tissue-specific damage in severe COVID-19.

systems biology↗

bioRxiv2019

Loss of microbial diversity and body site heterogeneity in individuals with Hidradenitis Suppurativa

Hidradenitis Suppurativa (HS) is a chronic, scarring, inflammatory skin disease affecting hair follicles in axillae, inguinal, and anogenital regions. Dysbiosis in HS patients compared to healthy subjects is documented. However, whether dysbiosis is specific to particular body sites or skin niches is unknown. We investigated the follicular and skin surface microbiome of the axilla and groin of HS patients (n=11) and healthy individuals (n=10) using 16S rRNA gene sequencing (V3-V4). We sampled non-lesional (HSN) and lesional skin (HSL) of HS patients. {beta}-diversity was significantly decreased (p<0.05) in HSN and HSL skin compared to normal skin with loss of body site and skin niche heterogeneity in HS samples. The relative bacterial abundance of specific microbes was also significantly different between normal and HSN (15 genera) or HSL (21 genera) skin. Smoking and alcohol use influenced the {beta}-diversity (p<0.08) in HS skin. We investigated metabolic profiles of bacterial communities in HS and normal skin using a computational approach. Metabolism, Genetic Information Processing, and Environmental Information Processing were significantly different between normal and HS samples. Altered metabolic pathways associated with dysbiosis of HS skin suggest mechanisms underlying the disease pathology and information about treatment with drugs targeting those pathways.

microbiology↗