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Objective: To introduce MexOMICS, a Mexican Consortium focused on establishing electronic databases to collect, cross-reference, and share health-related and omics data on the Mexican population., Methods: Since 2019, the MexOMICS Consortium has established three electronic-based registries: the Mexican Twin Registry (TwinsMX), Mexican Lupus Registry (LupusRGMX), and the Mexican Parkinson's Research Network (MEX-PD), designed and implemented using the Research Electronic Data Capture web-based application. Participants were enrolled through voluntary participation and on-site engagement with medical specialists. We also acquired DNA samples and Magnetic Resonance Imaging scans in subsets of participants., Results: The registries have successfully enrolled a large number of participants from a variety of regions within Mexico: TwinsMX ( n  = 2,915), LupusRGMX ( n  = 1,761) and MEX-PD ( n  = 750). In addition to sociodemographic, psychosocial, and clinical data, MexOMICS has collected DNA samples to study the genetic biomarkers across the three registries. Cognitive function has been assessed with the Montreal Cognitive Assessment in a subset of 376 MEX-PD participants. Furthermore, a subset of 267 twins have participated in cognitive evaluations with the Creyos platform and in MRI sessions acquiring structural, functional, and spectroscopy brain imaging; comparable evaluations are planned for LupusRGMX and MEX-PD., Conclusions: The MexOMICS registries offer a valuable repository of information concerning the potential interplay of genetic and environmental factors in health conditions among the Mexican population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Reyes-Pérez, Hernández-Ledesma, Román-López, García-Vilchis, Ramírez-González, Lázaro-Figueroa, Martinez, Flores-Ocampo, Espinosa-Méndez, Tinajero-Nieto, Peña-Ayala, Morelos-Figaredo, Guerra-Galicia, Torres-Valdez, Gordillo-Huerta, Gandarilla-Martínez, Salinas-Barboza, Félix-Rodríguez, Frontana-Vázquez, Matuk-Pérez, Estrada-Bellmann, Alpizar-Rodríguez, Rodríguez-Violante, Rentería, Ruíz-Contreras, Alcauter and Medina-Rivera.)

TwinsMX registry is a national research initiative in Mexico that aims to understand the complex interplay between genetics and environment in shaping physical and mental health traits among the country's population. With a multidisciplinary approach, TwinsMX aims to advance our knowledge of the genetic and environmental mechanisms underlying ethnic variations in complex traits and diseases, including behavioral, psychometric, anthropometric, metabolic, cardiovascular and mental disorders. With information gathered from over 2800 twins, this article updates the prevalence of several complex traits; and describes the advances and novel ideas we have implemented such as magnetic resonance imaging. The future expansion of the TwinsMX registry will enhance our comprehension of the intricate interplay between genetics and environment in shaping health and disease in the Mexican population. Overall, this report describes the progress in the building of a solid database that will allow the study of complex traits in the Mexican population, valuable not only for our consortium, but also for the worldwide scientific community, by providing new insights of understudied genetically admixed populations.

Astigmatism and myopia are two common ocular refractive errors that can impact daily life, including learning and productivity. Current knowledge suggests that the etiology of these conditions is the result of a complex interplay between genetic and environmental factors. Studies in populations of European ancestry have demonstrated a higher concordance of refractive errors in monozygotic (MZ) twins compared to dizygotic (DZ) twins. However, there is a lack of studies on genetically informative samples of multi-ethnic ancestry. This study aimed to estimate the genetic contribution to astigmatism and myopia in the Mexican population. A sample of 1399 families, including 243 twin pairs and 1156 single twins, completed a medical questionnaire about their own and their co-twin's diagnosis of astigmatism and myopia. Concordance rates for astigmatism and myopia were estimated, and heritability and genetic correlations were determined using a bivariate ACE Cholesky decomposition method, decomposed into A (additive genetic), C (shared environmental) and E (unique environmental) components. The results showed a higher concordance rate for astigmatism and myopia for MZ twins (.74 and .74, respectively) than for DZ twins (.50 and .55). The AE model, instead of the ACE model, best fitted the data. Based on this, heritability estimates were .81 for astigmatism and .81 for myopia, with a cross-trait genetic correlation of r A = .80, nonshared environmental correlation r E = .89, and a phenotypic correlation of r P = .80. These results are consistent with previous findings in other populations, providing evidence for a similar genetic architecture of these conditions in the multi-ethnic Mexican population.

A pipeline is proposed here to describe different features to study brain microcircuits on a histological scale using multi-scale analyses, including the uniform manifold approximation and projection (UMAP) dimensional reduction technique and modularity algorithm to identify neuronal ensembles, Runs tests to show significant ensembles activation, graph theory to show trajectories between ensembles, and recurrence analyses to describe how regular or chaotic ensembles dynamics are. The data set includes ex-vivo NMDA-activated striatal tissue in control conditions as well as experimental models of disease states: decorticated, dopamine depleted, and L-DOPA-induced dyskinetic rodent samples. The goal was to separate neuronal ensembles that have correlated activity patterns. The pipeline allows for the demonstration of differences between disease states in a brain slice. First, the ensembles were projected in distinctive locations in the UMAP space. Second, graphs revealed functional connectivity between neurons comprising neuronal ensembles. Third, the Runs test detected significant peaks of coactivity within neuronal ensembles. Fourth, significant peaks of coactivity were used to show activity transitions between ensembles, revealing recurrent temporal sequences between them. Fifth, recurrence analysis shows how deterministic, chaotic, or recurrent these circuits are. We found that all revealed circuits had recurrent activity except for the decorticated circuits, which tended to be divergent and chaotic. The Parkinsonian circuits exhibit fewer transitions, becoming rigid and deterministic, exhibiting a predominant temporal sequence that disrupts transitions found in the controls, thus resembling the clinical signs of rigidity and paucity of movements. Dyskinetic circuits display a higher recurrence rate between neuronal ensembles transitions, paralleling clinical findings: enhancement in involuntary movements. These findings confirm that looking at neuronal circuits at the histological scale, recording dozens of neurons simultaneously, can show clear differences between control and diseased striatal states: "fingerprints" of the disease states. Therefore, the present analysis is coherent with previous ones of striatal disease states, showing that data obtained from the tissue are robust. At the same time, it adds heuristic ways to interpret circuitry activity in different states., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation, though no other collaboration, with one of the author JB at the time of review., (Copyright © 2022 Serrano-Reyes, Pérez-Ortega, García-Vilchis, Laville, Ortega, Galarraga and Bargas.)

The mouse motor cortex exhibits spontaneous activity in the form of temporal sequences of neuronal ensembles in vitro without the need of tissue stimulation. These neuronal ensembles are defined as groups of neurons with a strong correlation between its firing patterns, generating what appears to be a predetermined neural conduction mode that needs study. Each ensemble is commonly accompanied by one or more parvalbumin expressing neurons (PV+) or fast spiking interneurons. Many of these interneurons have functional connections between them, helping to form a circuit configuration similar to a small-world network. However, rich club metrics show that most connected neurons are neurons not expressing parvalbumin, mainly pyramidal neurons (PV-) suggesting feed-forward propagation through pyramidal cells. Ensembles with PV+ neurons are connected to these hubs. When ligand-gated fast GABAergic transmission is blocked, temporal sequences of ensembles collapse into a unique synchronous and recurrent ensemble, showing the need of inhibition for coding cortical spontaneous activity. This new ensemble has a duration and electrophysiological characteristics of brief recurrent interictal epileptiform discharges (IEDs) composed by the coactivity of both PV- and PV+ neurons, demonstrating that GABA transmission impedes its occurrence. Synchronous ensembles are clearly divided into two clusters one of them lasting longer and mainly composed by PV+ neurons. Because an ictal-like event was not recorded after several minutes of IEDs recording, it is inferred that an external stimulus and/or fast GABA transmission are necessary for its appearance, making this preparation ideal to study both the neuronal machinery to encode cortical spontaneous activity and its transformation into brief non-ictal epileptiform discharges., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Different corticostriatal suprathreshold responses in direct and indirect striatal projection neurons (SPNs) of rodents have been reported. Responses consist in prolonged synaptic potentials of polysynaptic and intrinsic origin, in which voltage-gated Ca 2 ⁺ currents play a role. Recording simultaneous Ca 2 ⁺ imaging and voltage responses at the soma, while activating the corticostriatal pathway, we show that encoding of synaptic responses into trains of action potentials (APs) is different in SPNs: firing of APs in D1-SPNs increase gradually, in parallel with Ca 2 ⁺ entry, as a function of stimulus intensity. In contrast, D2-SPNs attain a maximum number of evoked spikes at low stimulus intensities, Ca 2 ⁺ entry is limited, and both remain the same in spite of increasing stimulus strength. Stimulus needs to reach certain intensity, to have propagated Ca 2 ⁺ potentials to the soma plus a sudden step in Ca 2 ⁺ entry, without changing the number of fired APs, phenomena never seen in D1-SPNs. Constant firing in spite of changing stimulus, suggested the involvement of underlying inactivating potentials. We found that Caᵥ3 currents contribute to Ca 2+ entry in both classes of SPNs, but have a more notable effect in D2-SPNs, where a low-threshold spike was disclosed. Blockade of Ca V 3 channels retarded the steep rise in firing in D2-SPNs. Inhibition block increased the number of spikes fired by D2-SPNs, without changing firing in D1-SPNs. These differences in synaptic integration enable a biophysical dissimilarity: dendritic inhibition appears to be more relevant for D2-SPNs. This may imply distinctions in the set of interneurons affecting each SPN class., (© 2018 Wiley Periodicals, Inc.)