Biology subjects

Lyon, M.

Publications and source records attributed to Lyon, M..

6 recordsLinked to original sources

bioRxiv2025

Comparative Cilia Analysis in the Cerebral Cortices of Turtles, Mice, and Macaques

Primary cilia are centriole-derived sensory organelles found in most vertebrate cells including neurons. In the mouse neocortex, the primary cilia of pyramidal neurons are found to orient predominantly toward the pia, reflecting a reverse movement that occurs during postnatal neuronal repositioning. This study compared cilia orientation in principal excitatory neurons in the cerebral cortex across turtles, mice, and macaques to identify patterns to infer mechanisms of cortical evolution. We first developed custom MATLAB Apps to facilitate the fast identification and statistical analyses of cilia orientation. We found that generally the primary cilia of principal neurons in sparse inside-out laminated regions, including the macaque and mouse neocortex, macaque CA1, mouse entorhinal cortex and neighboring regions, and mouse piriform cortex layer III, orient toward the pia. In contrast, primary cilia in compact laminae of these species, including the macaque and mouse dentate gyrus (DG), macaque CA3, mouse piriform cortex layer II, and turtle lateral cortex manifest opposite orientations, positioning perpendicular to the laminae. These data suggest that over the course of cortical evolution, primary cilia in principal neurons evolve from initially having no preferred orientation to becoming increasingly oriented toward the pial surface. We propose a working model for cortical evolution: the placement of principal neurons progresses from minimal migration in lower vertebrates to forward migration in higher species, and ultimately to pronounced reverse soma movement in higher inside-out laminated cortices, driven by the accumulation of large neuronal populations in the outer layers after completing radial migration.

neuroscience↗

bioRxiv2025

Reelin Controls the Directional Orientation, Apical Localization and Length of Primary Cilia in Principal Neurons in the Cerebral Cortex

The primary cilia of pyramidal neurons in inside-out laminated regions orient predominantly toward the pia, reflecting reverse soma movement during postnatal neurodevelopment. However, the mechanisms underlying the directional cilia orientation are unknown. Here we show that the primary cilia of pyramidal neurons are localized near the base of the apical dendrites and aligned on the nuclear side opposite to the axon initial segment (AIS). However, this pattern is not observed in atypical pyramidal neurons in the deep neocortex, excitatory neurons in non-laminated regions, interneurons, or astrocytes, where cilia are irregularly positioned around the nuclei and lack preferred orientation. In Reelin-deficient mice (reeler), the directional orientation and apical location of cilia in late-born neocortical and CA1 neurons are disrupted. However, the initial impairments are partially corrected during postnatal development, along with a realignment of apical-basal orientation. In contrast, loss of Reelin drastically disrupts the directional orientation of cilia in early-born neocortical neurons and principal neurons in evolutionarily conserved cortical regions, which lack postnatal correction. Consistently, their cilia do not preferably localize to the apical side. Additionally, Reelin deficiency increases the cilia length of principal neurons across the cerebral cortex at a developmental stage when cilia stabilize in wild-type mice, but this effect is not observed in interneurons, astrocytes, or excitatory neurons in non-laminated regions. Together, Reelin controls the directional orientation, apical localization, and length of primary cilia in principal neurons in the cerebral cortex, underscoring the cilium as a key apical domain particularly prominent in late-born neurons.

neuroscience↗

bioRxiv2023

Activity Hierarchy Measurement to Establish Trace Memory-eligible "Primed" Neurons

While it is known that associative memory is preferentially encoded by memory-eligible primed neurons, in vivo neural activity hierarchy has not been quantified and little is known about how such a hierarchy is established. Leveraging in vivo calcium imaging of hippocampal neurons on freely behaving mice, we developed the first method to quantify real-time neural activity hierarchy in the CA1 region. Neurons on the top of activity hierarchy are identified as primed neurons. In cilia knockout mice that exhibit severe learning deficits, the percentage of primed neurons is drastically reduced. We developed a simplified neural network model that incorporates simulations of linear and non-linear weighted components, modeling the synaptic ionic conductance of AMPA and NMDA receptors, respectively. We found that moderate non-linear to linear conductance ratios naturally leads a small fraction of neurons to be primed in the simulated neural network. Removal of the non-linear component eliminates the existing activity hierarchy and reinstate it to the network stochastically primes a new pool of neurons. Blockade of NMDA receptors by ketamine not only decreases general neuronal activity causing learning impairments, but also disrupts neural activity hierarchy. Additionally, ketamine-induced super-synchronized slow oscillation during anesthesia can be simulated if the non-linear NMDAR component is removed to flatten activity hierarchy. Together, this study develops a unique method to measure neural activity hierarchy and identifies NMDA receptors as a key factor that controls the hierarchy. It presents the first evidence suggesting that hierarchy disruption by NMDAR blockade causes dissociation and psychosis.

neuroscience↗

bioRxiv2022

A community driven GWAS summary statistics standard

Summary statistics from genome-wide association studies (GWAS) represent a huge potential for research. A challenge for researchers in this field is the access and sharing of summary statistics data due to a lack of standards for the data content and file format. For this reason, the GWAS Catalog hosted a series of meetings in 2021 with summary statistics stakeholders to guide the development of a standard format. The key requirements from the stakeholders were for a standard that contained key data elements to be able to support a wide range of data analyses, required low bioinformatics skills for file access and generation, to have easily accessible metadata, and unambiguous and interoperable data. Here, we define the specifications for the first version of the GWAS-SSF format, which was developed to meet the requirements discussed with the community. GWAS-SSF consists of a tab-separated data file with well-defined fields and an accompanying metadata file.

bioinformatics↗

bioRxiv2020

Eukarion-134 attenuates endoplasmic reticulum stress-induced mitochondrial dysfunction in human skeletal muscle cells

ABSTRACTMaladaptive endoplasmic reticulum (ER) stress is associated with modified reactive oxygen species (ROS) generation, altered mitochondrial bioenergetics, and oxidative damage; and is postulated as a potential mechanism involved in the underlying muscle weakness experienced by patients with myositis, an acquired autoimmune neuromuscular disease. In this study, we investigate the impact of ROS generation in an in vitro model of ER stress in skeletal muscle, using the ER stress inducer tunicamycin (24 hours) in presence or absence of a superoxide dismutase/catalase mimetic Eukarion (EUK)-134. ER stress activation, ROS generation, mitochondrial function, biogenesis, morphology and dynamics (fusion/fission) were examined. Tunicamycin induced maladaptive ER stress, validated by stimulation of GRP94, GRP78, CHOP, XBP-1, ERDJ4, and GADD34, which were mostly mitigated by EUK-134 at transcriptional level. ER stress triggered mitochondrial unfolded protein response and promoted mitochondrial dysfunction, described by substantial loss of mitochondrial membrane potential, as well as reduction of respiratory control ratio, reserve capacity, phosphorylating respiration, and coupling efficiency, which was ameliorated by EUK-134. ROS-mediated biogenesis and fusion of mitochondria was evident in presence of tunicamycin, which however, had high propensity of fragmentation, accompanied by upregulated mRNA levels of fission-related markers. Increased cellular ROS generation oxidative stress was observed in response to ER stress that was ameliorated in the presence of EUK-134, even though no changes in mitochondrial superoxide were noticeable. These findings suggest that targeting ROS generation using the superoxide dismutase/catalase mimetic EUK-134 can amend aspects of ER stress-induced changes in mitochondrial dynamics and function. Overall, this study suggests that in instances of chronic ER stress, such as in myositis, quenching ROS generation may be a promising therapy for muscle weakness and dysfunction.Competing Interest StatementThe authors have declared no competing interest.View Full Text

physiology↗

bioRxiv2018

Laboratory Methods Supporting Measles surveillance in Queensland, Australia, 2010-2017

Australia was officially recognised as having eliminated endemic measles circulation in 2014. Maintaining laboratory support for surveillance of vaccine-preventable diseases such as measles is an essential component of reaching and maintaining circulation-free status. Between 2010 and 2017 over 13,700 specimens were tested in our laboratory by real-time RT-PCR (RT-rPCR). Positive extracts from travellers were sequenced as required. Sequences were uploaded to GenBank and demonstrated the wide genetic variation expected from detection of MeV among virus introductions due to global travel. We describe the laboratory workflow employed in our laboratory between 2010 and 2017 for the sensitive detection of MeV infection, supporting high-quality surveillance.

microbiology↗