bioRxiv Science⌕ Search

Biology subjects

Soman, K.

Publications and source records attributed to Soman, K..

3 recordsLinked to original sources

Restoring the Multiple Sclerosis Associated Imbalance of Gut Indole Metabolites Promotes Remyelination and Suppresses Neuroinflammation

In multiple sclerosis (MS) the circulating metabolome is dysregulated, with indole lactate (ILA) being one of the most significantly reduced metabolites. We demonstrate that oral supplementation of ILA impacts key MS disease processes in two preclinical models. ILA reduces neuroinflammation by dampening immune cell activation as well as infiltration; and promotes remyelination and in vitro oligodendrocyte differentiation through the aryl hydrocarbon receptor (AhR). Supplementation of ILA, a reductive indole metabolite, restores the gut microbiomes oxidative/reductive metabolic balance by lowering circulating indole acetate (IAA), an oxidative indole metabolite, that blocks remyelination and oligodendrocyte maturation. The ILA-induced reduction in circulating IAA is linked to changes in IAA-producing gut microbiota taxa and pathways that are also dysregulated in MS. Notably, a lower ILA:IAA ratio correlates with worse MS outcomes. Overall, these findings identify ILA as a potential anti-inflammatory remyelinating agent and provide insights into the role of gut dysbiosis-related metabolic alterations in MS progression. One Sentence SummaryIndole lactate, a postbiotic metabolite reduced in MS, corrects gut microbiome metabolic imbalances associated with remyelination and neuroinflammation.

neuroscience↗

A Hierarchical Anti-Hebbian Network Model for the Formation of Spatial Cells in Three-Dimensional Space

Three dimensional (3D) spatial cells in the mammalian hippocampalformationare believed to support the existence of 3D cognitive maps. Modeling studies are crucial to comprehend the neural principles governing the formation of these maps, yet to date very few have addressed this topic in 3D space. Here, we present a hierarchical network model for the formation of 3D spatial cells using anti-hebbian network. Built on empirical data, the model accounts for the natural emergence of 3D place, border and grid-cells as well as a new type of previously undescribed spatial cell type which we call plane cells. It further explains the plausible reason behind the place and grid-cell anisotropic coding that has been observed in rodents and the potential discrepancy with the predicted periodic coding during 3D volumetric navigation. Lastly, it provides evidence for the importance of unsupervised learning rules in guiding the formation of higher dimensional cognitive maps.

neuroscience↗

A computational model that explores the effect of environmental geometries on grid cell representations

Grid cells are a special class of spatial cells found in the medial entorhinal cortex (MEC) characterized by their strikingly regular hexagonal firing fields. This spatially periodic firing pattern was originally considered to be invariant to the geometric properties of the environment. However, this notion was contested by examining the grid cell periodicity in environments with different polarity (Krupic et al 2015) and in connected environments (Carpenter et al 2015). Aforementioned experimental results demonstrated the dependence of grid cell activity on environmental geometry. Analysis of grid cell periodicity on practically infinite variations of environmental geometry imposes a limitation on the experimental study. Hence we analyze the grid cell periodicity from a computational point of view using a model that was successful in generating a wide range of spatial cells, including grid cells, place cells, head direction cells and border cells. We simulated the model in four types of environmental geometries such as: 1) connected environments, 2) convex shapes, 3) concave shapes and 4) regular polygons with varying number of sides. Simulation results point to a greater function for grid cells than what was believed hitherto. Grid cells in the model code not just for local position but also for more global information like the shape of the environment. The proposed model is interesting not only because it was able to capture the aforementioned experimental results but, more importantly, it was able to make many important predictions on the effect of the environmental geometry on the grid cell periodicity.

neuroscience↗