Biology subjects

Soriano, J.

Publications and source records attributed to Soriano, J..

8 recordsLinked to original sources

bioRxiv2025

Modular architecture confers robustness to damage and facilitates recovery in spiking neural networks modeling in vitro neurons

Impaired brain function is restored following injury through dynamic processes that involve synaptic plasticity. This restoration is supported by the brains inherent modular organization, which promotes functional separation and redundancy. However, it remains unclear how the modular structure interacts with synaptic plasticity, most notably in the form of spike-timing-dependent plasticity (STDP), to define the damage response and recovery efficiency. In this work, we numerically modeled the response and recovery to damage of a neuronal network in vitro bearing a modular structure. Consistent with the in vitro observations, the in silico numerical model effectively captured the decline and subsequent recovery of spontaneous activity following the injury. We revealed that the modular structure confers robustness to injury, minimizes the decrease in neuronal activity, and promotes recovery via STDP. Finally, using the reservoir computing framework, we show that information representation in the neuronal network improves with the recovery of synchronous activity. Our work provides an experimental-numerical platform for predicting recovery in damaged neuronal networks and may help developing effective models for brain injury.

neuroscience↗

bioRxiv2025

Variability vs Phenotype: multimodal analysis of Dravet Syndrome Brain Organoids powered by Deep Learning

Brain organoids (BO) have risen as a reliable model for neurodelopmental disorders (ND), reproducing human brain development milestones. However, their significant intra- and inter-organoid variability compromises their use in advanced tasks such as drug testing. Overcoming experimental variability is crucial for models prone to variation, like unguided BO. BO modelling in Dravet Syndrome, a late-onset epileptic ND, represents a great challenge since BO variability accumulates with time, when phenotype shows in vitro. Leveraging deep learning, we developed ImPheNet, a predictive tool grounded in BO live imaging datasets. ImPheNet accurately classified phenotypes and assessed drug toxicity in BO derived from DS, revealing differences between genotypes and upon antiseizure drug exposure. These results are supported by transcriptomic and functional data, revealing an excitatory-inhibitory imbalance during the maturation of DS organoids. Altogether, our DL-predictive live imaging strategy, ImPheNet, emerges as a powerful tool enhancing BO research and advancing ND treatments.

developmental biology↗

bioRxiv2024

Involvement of the cellular prion protein in seeding and spreading of sarkosyl-derived fractions of Alzheimer's disease in Prnp mutant mice and in the P301S transgenic tauopathy mice model

The natural cellular prion protein is known to play several roles during development and adult brain. Far from its pathological roles in prionopathies, the non-pathogenic cellular prion protein has been described as a receptor for several amyloid in oligomeric and prefibrillar forms. For some amyloids, specific domains of the protein play a crucial role in modulating amyloids cellular uptake and seeding properties. In most studies, the functions and the role of putative amyloid receptors have been analyzed by using brain extracts derived from human neurodegenerative patients. Another strategy has been to modify the genetic dosage of the natural prion protein in genetic models of different diseases. In this study, we take advantage of both approaches to examine whether this protein plays a role in the seeding and spreading of pathogenic tau. Our results point to a role of the natural prion protein in the emergence of pathogenic tau in a mouse model overexpressing the mutation P301S of the human tau gene. In contrast, its role is minor when sarkosyl-derived brain samples of Alzheimers disease are used. In fact, our results indicate that the use of this type of sample is not adequate to determine the role of a putative receptor in tau seeding and spreading.

neuroscience↗

bioRxiv2023

Microbial communities from lean or obese are differently shaped after apple fibres supplementation

BackgroundObese microbial communities differ from lean ones. Previous studies have shown how dietary fiber interventions target the gut microbiome and effectively attenuate obesity-related conditions. Nevertheless, the mechanisms by which dietary fibres shape the gut microbiota are not elucidated yet. This in-vitro study investigated the differences between lean and obese microbiota and how they responded to dietary interventions using a multi-omics approach. ResultsBy employing in vitro digestion followed by microcolonic fermentations, we exposed obese and lean microbial communities to apple as a representative complex food matrix, apple pectin as a soluble fiber, and cellulose as an insoluble fibe. Metagenomics and metabolomics data indicated that obese and lean individuals had distinct starting microbial communities and functions. After 24 hours of exposure to different feeding conditions, the diet-responsive bacteria modulated the composition and functionality of lean and obese microbial communities. In the obese, the results suggested different mechanisms among gut commensals with an opportunistic lifestyle, allowing them to maximize their energy production from substrates breakdown and produce a specific profile of gut microbial metabolites (GMMs). ConclusionAt the taxonomical and functional level, our results underscore that dietary fibres shape bacterial communities differently depending on their initial microbial composition. This modulation affects the production of GMMs. Eating foods high in fiber is recognised to promotes a healthy gut microbiome. However, the same intervention can result in varying metabolic profiles depending on the microbial communities, which may affect the host differently.

microbiology↗

bioRxiv2022

Rich dynamics and functional organization on topographically designed neuronal networks in vitro

Neuronal cultures are a prominent experimental tool to understand complex functional organization in neuronal assemblies. However, neurons grown on flat surfaces exhibit a strongly coherent bursting behavior with limited functionality. To approach the functional richness of naturally formed neuronal circuits, here we studied neuronal networks grown on polydimethylsiloxane (PDMS) topographical patterns shaped as either parallel tracks or square valleys. We followed the evolution of spontaneous activity in these cultures along 20 days in vitro using fluorescence calcium imaging. The networks were characterized by rich spatiotemporal activity patterns that comprised from small regions of the culture to its whole extent. Effective connectivity analysis revealed the emergence of spatially compact functional modules that were associated to both the underpinned topographical features and predominant spatiotemporal activity fronts. Our results show the capacity of spatial constraints to mold activity and functional organization, bringing new opportunities to comprehend the structure-function relationship in living neuronal circuits.

bioengineering↗

bioRxiv2021

Involvement of mechanical cues in the migration of Cajal-Retzius cells in the marginal zone during neocortical development

Emerging evidence points to coordinated action of chemical and mechanical cues during brain development. At early stages of neocortical development, angiogenic factors and chemokines such as CXCL12, ephrins, and semaphorins assume crucial roles in orchestrating neuronal migration and axon elongation of postmitotic neurons. Here we explore the intrinsic mechanical properties of the developing marginal zone of the pallium in the migratory pathways and brain distribution of the pioneer Cajal-Retzius cells. These pioneer neurons are generated in several proliferative regions in the developing brain (e.g., the cortical hem and the pallial subpallial boundary) and migrate tangentially in the preplate/marginal zone covering the upper portion of the neocortex. These cells play crucial roles in correct neocortical layer formation by secreting several molecules such as Reelin. Our results indicate that the motogenic properties of Cajal-Retzius cells and their perinatal distribution in the marginal zone are also modulated by both chemical and mechanical factors, by the specific mechanical properties of Cajal-Retzius cells, and by the differential stiffness of the migratory routes. Indeed, cells originating in the cortical hem display higher migratory capacities than those generated in the pallial subpallial boundary which may be involved in the differential distribution of these cells in the dorsal-lateral axis in the developing marginal zone.

neuroscience↗

bioRxiv2021

Behavioral deficits, learning impairment, and enhanced hippocampal excitability in co-isogenic PrnpZH3/ZH3 mice

BackgroundThe cellular prion protein (PrPC) has been associated with numerous cellular processes, such as cell differentiation and neurotransmission. Moreover, it was recently demonstrated that some functions were misattributed to PrPC since results were obtained from mouse models with genetic artifacts. Here we elucidate the role of PrPC in the hippocampal circuitry and its related functions, like learning and memory, using the new strictly co-isogenic Prnp0/0 mouse (PrnpZH3/ZH3). Behavioral and operant conditioning tests were performed to evaluate memory and learning capabilities. In vivo electrophysiological recordings were carried out at CA3-CA1 synapses in living behaving mice, and spontaneous neuronal firing and network formation were monitored in primary neuronal cultures of PrnpZH3/ZH3 vs. wild-type mice. ResultsResults showed decreased motility, impaired operant conditioning learning, and anxiety-related behavior in PrnpZH3/ZH3 animals. PrPC absence enhanced susceptibility to high-intensity stimulations and kainate-induced seizures. However, long-term potentiation (LTP) was not enhanced in the PrnpZH3/ZH3 hippocampus. In addition, we observed a delay in neuronal maturation and network formation in PrnpZH3/ZH3 cultures. ConclusionIn conclusion, PrPC mediates synaptic function and protects the synapse from excitotoxic insults. Its deletion might evoke a susceptible epileptogenic brain that would fail to perform highly cognitive-demanding tasks such as associative learning and anxiety-like behaviors.

neuroscience↗

bioRxiv2020

Isolation and characterization of Streptomyces bacteriophages and Streptomyces strains encoding biosynthetic arsenals

The threat to public health posed by drug-resistant bacteria is rapidly increasing, as some of healthcares most potent antibiotics are becoming obsolete. Approximately two-thirds of the worlds antibiotics are derived from natural products produced by Streptomyces encoded biosynthetic gene clusters. Thus, in order to identify novel gene clusters, we sequenced the genomes of four bioactive Streptomyces strains isolated from the soil in San Diego County and used Bacterial Cytological Profiling adapted for agar plate culturing in order to examine the mechanisms of bacterial inhibition exhibited by these strains. In the four strains, we identified 101 biosynthetic gene clusters. Some of these clusters were predicted to produce previously studied antibiotics; however, the known mechanisms of these molecules could not fully account for the antibacterial activity exhibited by the strains, suggesting that novel clusters might encode antibiotics. When assessed for their ability to inhibit the growth of clinically isolated pathogens, three Streptomyces strains demonstrated activity against methicillin-resistant Staphylococcus aureus. Additionally, due to the utility of bacteriophages for genetically manipulating bacterial strains via transduction, we also isolated four new phages (BartholomewSD, IceWarrior, Shawty, and TrvxScott) against S. platensis. A genomic analysis of our phages revealed nearly 200 uncharacterized proteins, including a new site-specific serine integrase that could prove to be a useful genetic tool. Sequence analysis of the Streptomyces strains identified CRISPR-Cas systems and specific spacer sequences that allowed us to predict phage host ranges. Ultimately, this study identified Streptomyces strains with the potential to produce novel chemical matter as well as integrase-encoding phages that could potentially be used to manipulate these strains.

microbiology↗