Biology subjects

Wirth, S.

Publications and source records attributed to Wirth, S..

5 recordsLinked to original sources

bioRxiv2025

Spatio-temporal dynamics of ingroup interactions in macaques

When sharing a space with others, many species including humans evolved a compromise regulating occupancy influenced by social determinants. For example, students in a classroom tend to sit close to their friends, keeping the same spots across days, revealing the social structure in the classroom. This place preference suggests that factors such as social hierarchy and affiliation can shape space utilization; contrasting with random walk models of agents moving at random in any given direction. Here, we asked whether spatial occupancy of macaques (Macaca fascicularis and M. mulatta) within a unisex group, reveals a structured space utilization beyond simple spatial affordance within the finite space. To this end, in two groups of four animals, we analyzed the simultaneously recorded positions of each individual while the group roamed in an enclosure. The data was gathered using automated devices that allow measuring accurate concomitant positions and calculate precise inter-individual distance, which is impossible in classical ethology even using GPS devices. Thus, our setup opens new possibilities using modelling approach, to characterize social interaction dynamics in small enclosures. We found that (1) The identity of each animal could be decoded from its individual pattern of spatial occupancy, revealing that each animal sustained a spatial footprint across multiple days. (2) Average distance between monkeys was a proxy of their social hierarchy, confirming that interpersonal distance is correlated to affiliation and dominance hierarchy. (3) Alternating the social context by removing one of the monkeys revealed that only removing the closest social partner influenced occupancy. (4) Finally, the distribution of distance between pairs of monkeys was bimodal and was modeled using random walk approach with an additional parameter reflecting propensity to stay in close proximity, which was again related to dominance hierarchy. These analyses reveal that space utilization is structured as a function of social determinants in macaques and simple modeling approach to further study group organization in neuro-ethological settings.

animal behavior and cognition↗

bioRxiv2024

A myelinic channel system for organelle transport to the glial-axonal junction

Myelin sheaths comprise compacted layers of oligodendroglial membrane wrapped spirally around axons. Each sheath, if imagined unwrapped, has a cytoplasm-filled space at its perimeter, linking it to the oligodendrocyte soma via a short process. By electron microscopy (EM), this space, which we term the myelinic channel system contains microtubules and membranous organelles, but whether these are remnants of development or serve a function is unknown. Performing live imaging of myelinating oligodendrocytes expressing fluorescent reporters, we found that the myelinic channel system serves microtubule-dependent organelle transport. Further, the intra-myelinic movement of peroxisomes was modulated by neuronal electrical activity in these mixed neural cell cultures. Loss of oligodendroglial Kif21b or CNP in vivo led to apparent stasis of myelin organelles and secondary axon pathology. This suggests that oligodendrocytes require motor transport in myelin to maintain axonal integrity.

neuroscience↗

bioRxiv2023

Linking place and view: Organizing space through saccades and fixations between primate posterior parietal cortex and hippocampus

Humans primarily rely on vision to explore and guide actions in spatial environments. The parietal cortex is thought to withhold a unified representation of the visual space allowing to direct saccades to salient cues, while the hippocampus provides a memory-based cognitive place map of the environment. Understanding how these two representations interact during navigation is a key question. To probe the link between view and place, we compared neural activity in the posterior parietal cortex and hippocampus of macaques navigating in a virtual maze. When analyzed as a function of the animals position in the virtual environment, more neurons in the parietal cortex displayed spatial selectivity compared to the hippocampus. We hypothesized that such modulation by self-position in the parietal cortex might stem from processing visual cues of the environment through exploratory saccades and fixations. However, we established that position-selectivity was not solely correlated with simple oculomotor dynamics. Rather, spatial selectivities in the PPC and the HPC originated from cells driven by direct fixations of maze paths or landmarks. However, while a substantial proportion of PPC and HPC cells displayed selectivity towards landmarks features, such as their side of appearance or their identity, we also revealed different task-related maze segmentation between regions. Indeed, when animal gazed at paths, activity in parietal cortex revealed anticipation of reward while that of the hippocampus suggested reward outcome processing. On the other hand, when animals gazed at a landmark already present in the field of view, parietal activity tended to occur close to intersections, while that of hippocampus was more spatially distributed. Finally, at the population level, neurons in both regions anticipated landmarks before they appeared in the field of view, suggesting a shared knowledge of the spatial layout and a collective active role in memory-guided visual exploration across regions. Taken together, these findings shed light on the neural processes that link place and view, through action- and memory-driven exploration of objects in space.

neuroscience↗

bioRxiv2023

Astrocytic uptake of posttranslationally modified amyloid-β leads to endolysosomal system disruption and induction of pro-inflammatory signaling

The disruption of astrocytic catabolic processes contributes to the impairment of amyloid-{beta} (A{beta}) clearance, neuroinflammatory signaling, and the loss of synaptic contacts in late-onset Alzheimers disease (AD). While it is known that the posttranslational modifications of A{beta} have significant implications on biophysical properties of the peptides, their consequences for clearance impairment are not well understood. It was previously shown that N-terminally pyroglutamylated A{beta}3(pE)-42, a significant constituent of amyloid plaques, is efficiently taken up by astrocytes, leading to the release of pro-inflammatory cytokine tumor necrosis factor (TNF) and synapse loss. Here we report that A{beta}3(pE)-42, but not A{beta}1-42, gradually accumulates within the astrocytic endolysosomal system, disrupting this catabolic pathway and inducing formation of heteromorphous vacuoles. This accumulation alters lysosomal kinetics and lysosome-dependent calcium signaling, and upregulates lysosomal stress response. These changes correlate with the upregulation of glial fibrillary acidic protein (GFAP) and increased activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NFB). Treatment with a lysosomal protease inhibitor, E64, rescues GFAP upregulation, NFB activation, and synapse loss, indicating that abnormal lysosomal protease activity is upstream of pro-inflammatory signaling and related synapse loss. Collectively, our data suggest that A{beta}3(pE)-42-induced disruption of the astrocytic endolysosomal system leads to cytoplasmic leakage of lysosomal proteases, promoting pro-inflammatory signaling and synapse loss, hallmarks of AD-pathology.

neuroscience↗

bioRxiv2023

A common gene signature of the right ventricle in failing rat and human hearts

The molecular mechanisms of progressive right heart failure are incompletely understood. We systematically compared rat models of pulmonary artery or aortic banding to identify the transcriptomic changes that occur over months in the failing right versus left ventricle. Detailed bioinformatics analyses of 181 RNAseq datasets from cardiomyocytes or whole heart samples from these models, led to the identification of gene signatures, protein, and transcription factor networks specific to ventricles, compensated or decompensated disease states and type of heart failure. RNA-FISH approaches confirmed PAB-mediated regulation of key genes and revealed striking, spatially heterogeneous mRNA expression in the heart. Intersection of rat PAB-specific gene sets with 95 transcriptome data sets from human patients with chronic thromboembolic pulmonary hypertension led to the identification of more than 50 genes whose expression levels strongly correlated with the severity of right heart disease. Together, these data define a conserved, differentially regulated genetic network that coordinates progressive right heart failure in rats and humans. HighlightsO_LISide-by-side comparisons of RV or LV transcriptomes in the slowly failing rat heart C_LIO_LIIdentification of RV-specific gene sets in heart hypertrophy versus heart failure C_LIO_LIIdentification of RV gene sets correlating with severity of human CTEPH C_LIO_LIDevelopment of a core gene signature characteristic for RV failure C_LI

genomics↗