Biology subjects

Guillamon, A.

Publications and source records attributed to Guillamon, A..

4 recordsLinked to original sources

bioRxiv2026

Estimation of the time course of excitatory and inhibitory conductance during oscillatory periods

Determining the amount of information a neuron receives per unit of time is key to understanding brain connectivity and how neural networks encode and transmit information. In particular, estimating this information flow by distinguishing between excitatory and inhibitory synaptic contributions is critical to understanding neural network function, as maintaining the excitation-inhibition (E/I) balance regulates neuronal excitability and circuit stability, whereas its disruption can lead to a plethora of brain disorders, including neurodegenerative and psychiatric conditions. However, because synaptic conductances cannot be measured directly, inverse methods are required to infer them from the membrane potential --a readily measurable quantity. Although partial solutions have been proposed, accurately estimating these conductances remains a significant challenge due to the complexity and diversity of the inputs. This is particularly true in the spiking regime, where neurons actively fire. In this work, we introduce a novel computational strategy that combines two critical metrics extracted from the time course of the membrane potential recording: the amplitude of the spike and the interspike interval. By using these quantities, the proposed method enables the accurate separation of excitatory and inhibitory contributions, yielding highly favorable results in the spiking regime.

neuroscience↗

bioRxiv2021

The gendered self: Evidence for differences in whole-brain dynamics

How the brain constructs gender identity is largely unknown, but some neural differences have recently been discovered. Here, we used an intrinsic-ignition framework to investigate if gender identity changes the propagation of the neural activity across the whole-brain network and within resting-state networks. Studying 29 transmen and 17 transwomen with gender incongruence, 22 ciswomen, and 19 cismen, we computed the capability of a given brain area in space to propagate activity to other areas (mean-ignition) and its variability across time (node-metastability). We found that both measures differentiated all four groups across the whole-brain network. Furthermore, at the network level, we found that compared to the other groups, cismen showed higher mean-ignition of the dorsal attention network and node-metastability of the dorsal and ventral attention, executive control, and temporal parietal networks. We also found mean-ignition differences between cismen and ciswomen within the executive control network, but higher in ciswomen than cismen and transmen for the default-mode network. For the node-metastability, this was higher in cismen compared to ciswomen in the somatomotor network, while both mean-ignition and node-metastability were higher for cismen than transmen in the limbic network. Finally, we computed correlations between both measures and their body image scores. Transmen dissatisfaction, cismen, and ciswomen satisfaction towards their own body image were distinctively associated with specific networks per group. Overall, the study of the whole-brain network dynamical complexity discriminates binary gender identity groups, and functional connectivity dynamics approaches are needed to disentangle the complex understanding of the gendered self. Significance statementThe study of sex/gender differences may be enriched by the heterogeneity of other gender minority groups, such as transgender. Functional connectivity measures capturing the spatio-temporal oscillations of the brain can provide insights on how the brain cooperates. This is the first study investigating how the whole-brain network propagates information across the brain, spatially and temporally, in binary gender groups (cisgender and transgender) by means of the intrinsic-ignition framework. We found four whole-brain unique phenotypes pertaining to each gender group, namely cismen, ciswomen, transmen and transwomen. Novel functional connectivity dynamics frameworks can contribute to disentangle the complex experience of a gendered-self.

neuroscience↗

bioRxiv2020

Engineering self-organized criticality in living cells

Complex dynamical fluctuations, from molecular noise within cells, collective intelligence, brain dynamics or computer traffic have been shown to display noisy behaviour consistent with a critical state between order and disorder. Living close to the critical point can have a number of adaptive advantages and it has been conjectured that evolution could select (and even tend to) these critical states. One way of approaching such state is by means of so called self-organized criticality (SOC) where the system poises itself close to the critical point. Is this the case of living cells? It is difficult to test this idea given the enormous dimensionality associated with gene and metabolic webs. In this paper we present an alternative approach: to engineer synthetic gene networks displaying SOC behaviour. This is achieved by exploiting the presence of a saturation (congestion) phenomenon of the ClpXP protein degradation machinery in E. coli cells. Using a feedback design that detects and then reduces ClpXP congestion, a critical motif is built from a two-gene network system, where SOC can be successfully implemented. Both deterministic and stochastic models are used, consistently supporting the presence of criticality in intracellular traffic. The potential implications for both cellular dynamics and designed intracellular noise are discussed.

bioengineering↗

bioRxiv2020

Bivalent chromatin as a therapeutic target in cancer: An in silico predictive approach for combining epigenetic drugs

Tumour cell heterogeneity is a major barrier for efficient design of targeted anti-cancer therapies. A diverse distribution of phenotypically distinct tumour-cell subpopulations prior to drug treatment predisposes to non-uniform responses, leading to the elimination of sensitive cancer cells whilst leaving resistant subpopulations unharmed. Few strategies have been proposed for quantifying the variability associated to individual cancer-cell heterogeneity and minimizing its undesirable impact on clinical outcomes. Here, we report a computational approach that allows the rational design of combinatorial therapies involving epigenetic drugs against chromatin modifiers. We have formulated a stochastic model of a bivalent transcription factor that allows us to characterise three different qualitative behaviours, namely: bistable, high- and low-gene expression. Comparison between analytical results and experimental data determined that the so-called bistable and high-gene expression behaviours can be identified with undifferentiated and differentiated cell types, respectively. Since undifferentiated cells with an aberrant self-renewing potential might exhibit a cancer/metastasis-initiating phenotype, we analysed the efficiency of combining epigenetic drugs against the background of heterogeneity within the bistable sub-ensemble. Whereas single-targeted approaches mostly failed to circumvent the therapeutic problems represented by tumour heterogeneity, combinatorial strategies fared much better. Specifically, the more successful combinations were predicted to involve modulators of the histone H3K4 and H3K27 demethylases KDM5 and KDM6A/UTX. Those strategies involving the H3K4 and H3K27 methyltransferases MLL2 and EZH2, however, were predicted to be less effective. Our theoretical framework provides a coherent basis for the development of an in-silico platform capable of identifying the epigenetic drugs combinations best-suited to therapeutically manage non-uniform responses of heterogenous cancer cell populations. Author summaryHeterogeneity in cancer cell populations is one of the main engines of resistance to targeted therapies, as it induces nonuniform responses within the population that clears the sensitive subpopulation, whilst leaving unaffected the non-responsive cells. Although this is a well-known fact, few successful approaches have been proposed aimed at both quantifying the variability associated to cell heterogeneity, and characterising strategies that circumvent its drug-resistance inducing effects. Here we present a computational approach that addresses these issues in the particular context of targeting epigenetic regulators (specifically, chromatin modifiers), which have been proposed as therapeutic targets in several types of cancer and also in ageing-related diseases. Our model predicts that the more successful combinations involve modulators of demethylase activity (specifically, KDM5/6 and UTX). By contrast, strategies involving EZH2 activity are predicted to be less effective. Our results support the use of our framework as a platform for in silico drug trials, as it accounts for non-homogeneous response of cell populations to drugs as well as identifying which subpopulations are more likely to respond to specific strategies.

systems biology↗