Biology subjects

Woods, S.

Publications and source records attributed to Woods, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Disordered brain circuits linked to diagnostic specificity and comorbidity revealed by multivariate symptom modeling

Modeling how functional network connectivity underlies transdiagnostic symptomatology has promised to advance psychiatric medicine by revealing neurobiological mechanisms related to comorbidity. However, network mapping methods have yet to yield clinically-actionable insights, largely due to complexities in the neurobiological underpinnings of symptom comorbidity across disorders and symptom heterogeneity within disorders. Here, we sought to address this problem by leveraging a large (n=317) transdiagnostic dataset of adults with extensive fMRI scanning (>50 min), using connectome-based predictive modeling (CPM) to identify network correlates of an array of psychiatric symptoms. The symptom networks spanned a complex web of shared and unique networks, in which individuals displayed significant heterogeneity in their edge-level dysfunction. We then constructed disordered circuit models that jointly accounted for an individuals symptom severity, the multivariate network space, and network heterogeneity. Although all the symptoms were highly comorbid and none showed specificity to any single diagnostic category, many features within the disordered circuit models were uniquely associated with individual diagnoses and comorbidity patters. These findings shed mechanistic insights into how transdiagnostic symptoms arise from different neurobiological processes depending on a patients diagnostic profile. Thus, this approach provides key insights into where an individuals disordered circuits are located, a critical first step in precision psychiatry frameworks.

neuroscience↗

bioRxiv2026

Shedding light on YfhS and YjlC: novel effectors of the NADH dehydrogenase activity of the electron transport chain in Bacillus subtilis

Oxidative phosphorylation is the most efficient way of generating ATP in respiring cells. As high energy electrons are the major source of reactive oxygen species their production needs to be carefully calibrated. In most organisms, NADH dehydrogenase serves as the primary source and gateway of electrons. This complex is responsible for oxidizing NADH to NAD+, which liberates two electrons that are then fed into the respiratory chain. In the Gram-positive model bacterium, Bacillus subtilis, a transcription factor (Rex) is utilized to monitor the rise in NADH level and subsequently increase the production of the NADH dehydrogenase Ndh. Thus, the generation of electrons through this pathway is tightly regulated. In this report, we reveal the presence of another independent mechanism to moderate Ndh activity involving a previously uncharacterized protein, YfhS. Additionally, we present the first experimental evidence showing that the functional NADH dehydrogenase is a two-protein complex comprised of a membrane-associated YjlC and the enzyme Ndh. We find that absence of YfhS leads to cell morphology and growth defects that are corrected by spontaneous mutations in ndh. We note that increased production of NADH dehydrogenase complex proteins by itself is not detrimental. However, strikingly, it is lethal in a strain lacking yfhS. These results reveal that YfhS is an important moderator of NADH dehydrogenase activity. We also demonstrate that YfhS and YjlC are interaction partners. A model developed based on our data indicates that YfhS is an important regulator of intracellular NADH concentration. Compounds that target specific microbial (Type II) NADH dehydrogenase, which is absent in human mitochondria, are considered promising drug candidates to help address the threat posed by antibiotic-resistant bacteria. Overall, our data unveiling the importance of YfhS and YjlC in controlling Ndh activity could be harnessed for the development of new therapeutics.

microbiology↗

bioRxiv2025

Human pluripotent stem cell model of multiple epiphyseal dysplasia with MATN3 mutation identifies altered Matrix organisation and upregulation of the cholesterol biosynthesis pathway

Multiple epiphyseal dysplasia (MED), caused by mutations in MATN3, is a chondrodysplasia affecting the cartilage growth plate and is characterised by delayed epiphyseal ossification, short stature, and early onset osteoarthritis. Here we generated an in vitro human pluripotent stem cell (hPSC) model of cartilage growth-plate development to identify pathogenic mechanisms underlying MED. hPSCs were differentiated to chondrocytes via a mesenchymal intermediate, followed by TGF{beta}3+BMP2 induced chondrogenic pellet culture. MATN3-mutant hPSCs were generated by reprogramming MED patient PBMCs or by CRISPR-Cas9 gene editing to introduce a MATN3 mutation in a hESC line. RNAseq was used to assess chondrogenesis and identify MED pathogenic mechanisms. Transmission electron microscopy (TEM) was used to assess extracellular matrix assembly. The resultant hPSC-derived cartilage pellets displayed a typical cartilage morphology and strongly expressed cartilage matrix markers, e.g., collagen II and matrilin-3. Matrilin-3 protein was detected within both the matrix and cells of heterozygous mutant hPSC-cartilage pellets. RNAseq of mutant hPSC-cartilage pellets revealed significant enrichment for ECM organisation and cholesterol biosynthesis pathway genes as well as sightly increased expression of some unfolded protein response (UPR) marker genes. MATN3 mutant hPSC-derived cartilage pellets displayed abnormal matrix assembly, distended ER, accumulation of lipid droplets, and increased cholesterol content. Our model revealed mutant matrilin-3 induces cholesterol biosynthesis pathway upregulation and abnormal matrix assembly during MED pathogenesis. This study provides new insights into the molecular mechanisms underlying MED and highlights potential therapeutic targets.

cell biology↗

bioRxiv2025

Genome editing of a low-penetrance albinism-associated variant in TYR in patient-derived pluripotent stem cells

TYR encodes tyrosinase, the enzyme catalysing the initial steps of melanin biosynthesis in melanocytes and retinal pigment epithelia (RPE). TYR c.1205G>A (p.Arg402Gln) is a common genetic variant associated with several pigmentation traits. Notably, when this variant is encountered in specific haplotypic backgrounds in the homozygous state, it predisposes to albinism. We generated an induced pluripotent stem cell (iPSC) line from an affected individual carrying such a homozygous genotype (UMANi255-A), and then used CRISPR-Cas9 to correct the TYR c.1205G>A variant (UMANi255-A-1). The resulting iPSC lines demonstrate capacity for multi-lineage differentiation, providing a useful in vitro model for studying pigmentation biology.

cell biology↗

bioRxiv2024

Adaptation and acclimation of gametophytic traits to heat stress in a widely distributed wild plant along a steep climatic gradient

O_LIClimate change-induced heat waves often result in reduced seed yields and quality via high-temperature effects in the gametophytic phase. Surprisingly, the ability of pollen and ovules, particularly among wild plant populations, to adapt or acclimate to heat stress remains poorly understood. C_LIO_LITo address this gap, we examined the adaptive and acclimation potential of six gametophytic traits in eleven distinct populations of wild Silene vulgaris across a temperature gradient in Europe. First, we cultivated plants in a common garden to reveal differences in gametophytic traits indicative of adaptation. Next, we assessed the acclimation potential of these traits to heat stress by subjecting flowering plants to two chronic heat stress (CHS) treatments: moderate (35/30 {degrees}C) and severe (40/35 {degrees}C), for 18 days. C_LIO_LIFindings from the common garden experiment indicated no intraspecific variation in gametophytic traits across the temperature gradient, suggesting that these traits may not influence the plants sexual adaptation to its local habitat. Plants originating from colder climates produced more and larger seeds than those from warmer climates. During CHS treatments, the female gametophyte was less temperature sensitive compared to the male gametophyte. Moderate CHS led to larger ovaries with more, large-sized ovules, while severe CHS reduced ovule numbers but increased their size. In contrast, both CHS treatments decreased pollen grain numbers, size, and anther length, with severe CHS causing more significant reductions. These reductions in gametophytic traits ultimately translated to lower seed yield and quality, which may threaten the sustained existence of natural plant populations over time. Under both CHS treatments, the acclimation potential did not vary among plant populations along the temperature gradient, except for pollen size under severe CHS, with larger pollen size in warmer climates than in colder regions. C_LIO_LIOur findings suggest that the lack of adaptation and acclimation mechanisms in the gametophytic traits (except for pollen size) of wild Silene vulgaris populations along the temperature gradient indicates that these plants may rely on alternative strategies, such as shifts in flowering time, to respond to thermal stress. C_LI

plant biology↗

bioRxiv2024

Testing the Tests: Using Connectome-Based Predictive Models to Reveal the Systems Standardized Tests and Clinical Symptoms Are Reflecting

BackgroundSubstantial strides have been made in developing connectome-based predictive models that establish connections between external measures of cognition and/or symptoms obtained through testing performed in a clinical setting, and the human functional connectome. Often referred to as brain-behavior modeling such models offer insights into the functional brain organization supporting the test scores of these external measures1-7. Here, we depart from the conventional feed-forward approach and introduce a feed-back approach that provides new insight into the systems the external measures are reflecting and provides a framework for developing new test instruments that better target specific brain systems. MethodsIn fMRI data from 227 demographically and clinically diverse subjects (healthy participants and patients), we a priori define connectivity networks for the six cognitive constructs and employ kernel ridge regression in a predictive modeling framework to quantify each networks contribution to performance across a spectrum of standardized tests. ResultsThis approach provides a ranking of test scores according to the predictive power of each cognitive network, allowing one to choose the best test to probe a specific brain network. It yields a brain-driven process for forming new tests through selection of combinations of measures that probe the same brain systems. These new composite tests yield better external measures, as reflected by higher predictive power in brain-behavior modeling. We also evaluate the inclusion of specific subtests within a composite score, revealing instances where composite scores are reinforced or weakened by subtest inclusion regarding the specificity of the brain network they interrogate. ConclusionsThe brain-behavior modeling problem can be reconfigured to provide a biologically driven approach to the selection of external measures directed at specific brain systems. It opens new avenues of research by providing a framework for the development of measures, both cognitive and clinical, guided by quantitative brain metrics.

neuroscience↗

bioRxiv2023

Single cell transcriptomics reveals chondrocyte differentiation dynamics in vivo and in vitro

The consistent production of in vitro chondrocytes that faithfully recapitulate in vivo development would be of great benefit for musculoskeletal disease modelling and regenerative medicine. Current efforts are often limited by off-target differentiation, resulting in a heterogeneous product. Furthermore, the lack of comparison to human embryonic tissue, precludes detailed evaluation of in vitro cells. Here, we perform single-cell RNA sequencing of embryonic long bones dissected from first trimester hind limbs from a range of gestational ages. We combine this with publicly available data to form a detailed atlas of endochondral ossification, which we then use to evaluate a series of published in vitro chondrogenesis protocols, finding substantial variability in cell states produced by each. We apply single-nuclear RNA sequencing to one protocol to enable direct comparison between in vitro and in vivo, and perform trajectory alignment between the two to reveal differentiation dynamics at the single-cell level, shedding new light on off-target differentiation in vitro. Using this information, we inhibit the activity of FOXO1, a transcription factor predicted to be active in embryonic bone development and in chondrogenic cells in vitro, and increase chondrocyte transcripts in vitro. This study therefore presents a new framework for evaluating tissue engineering protocols, using single-cell data from human development to drive improvement and bring the prospect of true engineered cartilage closer to reality.

bioengineering↗

bioRxiv2023

Effect of a retinoic acid analogue on BMP-driven pluripotent stem cell chondrogenesis

Osteoarthritis is the most common degenerative joint condition, leading to articular cartilage (AC) degradation, chronic pain and immobility. The lack of appropriate therapies that provide tissue restoration combined with the limited lifespan of joint-replacement implants indicate the need for alternative AC regeneration strategies. Differentiation of human pluripotent stem cells (hPSCs) into AC progenitors may provide a long-term regenerative solution but are still limited due to the continued reliance upon growth factors to recapitulate developmental signalling processes. Recently, TTNPB, a small molecule activator of retinoic acid receptors (RARs), has been shown to be sufficient to guide mesodermal specification and early chondrogenesis of hPSCs. Here, we modified our previous differentiation protocol, by supplementing cells with TTNPB and administering BMP2 at specific times to enhance early development. Transcriptomic analyses indicated that activation of RAR signalling significantly upregulated genes related to limb and embryonic skeletal development in the early stages of the protocol and upregulated genes related to AC development in later stages. Chondroprogenitors obtained from RAPID-E could generate cartilaginous pellets that expressed AC-related matrix proteins such as Lubricin, Aggrecan, and Collagen II. This protocol could lay the foundations for cell therapy strategies for osteoarthritis and improve the understanding of AC development in humans.

developmental biology↗

bioRxiv2023

Human pluripotent stem cell-derived kidney organoids reveal tubular epithelial pathobiology of heterozygous HNF1B-associated dysplastic kidney malformations

Hepatocyte nuclear factor 1B (HNF1B) encodes a transcription factor expressed in developing human kidney epithelia. Heterozygous HNF1B mutations are the commonest monogenic cause of dysplastic kidney malformations (DKMs). To understand their pathobiology, we generated heterozygous HNF1B mutant kidney organoids from CRISPR-Cas9 gene-edited human ESCs and iPSCs reprogrammed from a family with HNF1B-asscociated DKMs. Mutant organoids contained enlarged malformed tubules and displayed deregulated cell turnover. Numerous genes implicated in Mendelian kidney tubulopathies were downregulated, and mutant tubules resisted the cAMP-mediated dilatation seen in controls. Bioinformatic analyses indicated abnormal WNT, calcium, and glutamatergic pathways, the latter hitherto unstudied in developing kidneys. Glutamate ionotropic receptor kainate type subunit 3 was upregulated in mutant organoids and was detected in their tubules and in fetal human DKM dysplastic epithelia. These results reveal morphological, molecular, and physiological roles for HNF1B in human kidney tubule morphogenesis and functional differentiation. They additionally suggest druggable targets to ameliorate disease.

developmental biology↗

bioRxiv2021

Why do hippocampal mossy cells matter? It depends on the frequency and context.

The discrimination of similar episodes and places, and their representation as distinct memories, depend on a process called pattern separation that relies on the circuitry of the hippocampal dentate gyrus (DG). Mossy cells (MCs) are key neurons in the circuitry, but how they influence DG network dynamics, function, and seizure risk has not been fully elucidated. We found the net impact of MCs was inhibitory at physiological frequencies connected with learning and behaviour, and their absence associated with deficits in pattern separation and spatial memory; at higher frequencies, their net impact was excitatory, and their absence protected against seizures. Thus, MCs influence DG outputs in a highly dynamic manner that varies with frequency and context. One-Sentence SummaryHippocampal mossy cells are required for learning and memory; but their absence protects against seizures.

neuroscience↗

bioRxiv2021

Kidney organoids: A system to study human basement membrane assembly in health and disease

Basement membranes (BMs) are complex macromolecular networks underlying all continuous layers of cells. Essential components include type IV collagen and laminins, which are affected by human genetic defects leading to a range of debilitating conditions including kidney, muscle, and cerebrovascular phenotypes. We investigated the dynamics of BM assembly in human pluripotent stem cell-derived kidney organoids. We resolved their global BM composition and discovered a conserved temporal sequence in BM assembly that paralleled mammalian fetal kidneys. We identified the emergence of key BM isoforms, which were altered by a pathogenic variant in COL4A5. Integrating organoid, fetal and adult kidney proteomes we found dynamic regulation of BM composition through development to adulthood, and with single-cell transcriptomic analysis we mapped the cellular origins of BM components. Overall, we define the complex and dynamic nature of vertebrate BM assembly and provide a platform for understanding its wider relevance in human development and disease.

cell biology↗

bioRxiv2021

Versioning Biological Cells for Trustworthy Cell Engineering

"Full-stack" biotechnology platforms for cell line (re)programming are on the horizon, due mostly to (a) advances in gene synthesis and editing techniques as well as (b) the growing integration with informatics, the internet of things and automation. These emerging platforms will accelerate the production and consumption of biological products. Hence, transparency, traceability and -ultimately-trustworthiness is required -from cradle to grave- for engineered cell lines and their engineering processes. We report here the first version control system for cell engineering that integrates a new cloud-based version control software for cell lines digital footprint with molecular barcoding of living samples. We argue that version control for cell engineering marks a significant step towards more open, reproducible, easier to trace and share, and more trustworthy engineering biology. One Sentence SummaryWe demonstrate a transparent and open way of engineering and sharing cell lines.

synthetic biology↗

bioRxiv2021

Frog nest foam as a drug delivery system

Foams have frequently been used as systems for the delivery of cosmetic and therapeutic molecules; however, there is high variability in the foamability and long-term stability of synthetic foams. The development of pharmaceutical foams that exhibit desirable foaming properties, delivering appropriate amounts of the active pharmaceutical ingredient (API) and that have excellent biocompatibility is of great interest. The production of stable foams is rare in the natural world; however, certain species of frogs have adopted foam production as a means of providing a protective environment for their eggs and larvae from a predators and parasites, to prevent desiccation, to control gaseous exchange, temperature extremes, and to reduce UV damage. These foams show great stability (up to 10 days in tropical environments) and are highly biocompatible due to the sensitive nature of amphibian skin. This work demonstrates for the first time, that nests of the Tungara frog (Engystomops pustulosus) is stable ex situ with useful physiochemical and biocompatible properties and is capable of encapsulating a range of compounds, including antibiotics. These protein foam mixtures share some properties with pharmaceutical foams and may find utility in a range of pharmaceutical applications such as a topical drug delivery systems (DDS).

bioengineering↗

bioRxiv2020

Feeding dihydroquercetin and vitamin E to broiler chickens reared at standard and high ambient temperatures

The use of natural antioxidants, in particular polyphenols such as dihydroquercetin (DHQ), in animal nutrition have recently increased in popularity. This may partly be due to the risk of increased incidences of heat stress associated with raising livestock in warmer ambient temperatures, facilitated by global warming, reducing antioxidant capacity. The current research demonstrates the effect of dietary DHQ, vitamin E and standard or high ambient temperatures on growth performance, energy and nutrient metabolism, gastrointestinal tract development (GIT), jejunal villus morphometry and antioxidant status in broiler chickens. Each of the four experimental diets were fed to 16 pens of five birds, which were allocated to four rooms (four pens in each room). The temperature in two rooms was maintained at a constant 35 {degrees}C (high temperature; HT), and the temperature in the other two rooms was gradually reduced from 27 {degrees}C at 7d of age to 22 {degrees}C at 20d of age (standard temperature; ST). Rearing birds at HT reduced: feed intake, weight gain, weight of small intestine, total GIT, liver, spleen, heart, villus height, villus surface area and lowered blood glutationperoxidase (GSH-Px). Dietary DHQ increased blood GSH-Px and total antioxidant status, increased heart weight and reduced caecal size. When fed separately, DHQ and vitamin E improved hepatic vitamin E concentration. Feeding vitamin E increased spleen and liver weights. When fed together, DHQ and vitamin E reduced villus height, villus height to crypt depth ratio and villus surface area. Temperature and antioxidants did not affect energy and nutrient metabolism. There were no effects of dietary antioxidants on growth performance of broiler chickens and there were no mortalities. At present it is unclear if feeding antioxidants (in particular DHQ) at different levels, using different dietary formulations, and rearing birds under a range of environmental conditions may be effective at enhancing production performance and bird health in hot ambient climates.

physiology↗

bioRxiv2020

Modelling the developmental spliceosomal craniofacial disorder Burn-McKeown syndrome using induced pluripotent stem cells

The craniofacial developmental disorder Burn-McKeown Syndrome (BMKS) is caused by biallelic variants in the pre-messenger RNA splicing factor gene TXNL4A/DIB1. The majority of affected individuals with BMKS have a 34 base pair deletion in the promoter region of one allele of TXNL4A combined with a loss-of-function variant on the other allele, resulting in reduced TXNL4A expression. However, it is unclear how reduced expression of this ubiquitously expressed spliceosome protein results in craniofacial defects during development. Here we reprogrammed peripheral mononuclear blood cells from a BMKS patient and her unaffected mother into induced pluripotent stem cells (iPSCs) and differentiated the iPSCs into induced neural crest cells (iNCCs), the key cell type required for correct craniofacial development. BMKS patient-derived iPSCs proliferated more slowly than both mother- and unrelated control-derived iPSCs, and RNA-Seq analysis revealed significant differences in gene expression and alternative splicing. Patient iPSCs displayed defective differentiation into iNCCs compared to maternal and unrelated control iPSCs, in particular a delay in undergoing an epithelial-to-mesenchymal transition (EMT). RNA-Seq analysis of differentiated iNCCs revealed widespread gene expression changes and mis-splicing in genes relevant to craniofacial and embryonic development that highlight a dampened response to WNT signalling, the key pathway activated during iNCC differentiation. Furthermore, we identified the mis-splicing of TCF7L2 exon 4, a key gene in the WNT pathway, as a potential cause of the downregulated WNT response in patient cells. Additionally, mis-spliced genes shared common sequence properties such as length, splice site strengths and sequence motifs, suggesting that splicing of particular subsets of genes is particularly sensitive to changes in TXNL4A expression. Together, these data provide the first insight into how reduced TXNL4A expression in BMKS patients might compromise splicing and NCC function, resulting in defective craniofacial development in the embryo.

genetics↗

bioRxiv2020

Optogenetic control of the Bone Morphogenetic Protein signalling pathway through engineered blue light-sensitive receptors

Bone Morphogenetic Proteins (BMPs) are members of the Transforming Growth Factor {beta} (TGF{beta}) superfamily and have crucial roles during development; including mesodermal patterning and specification of renal, hepatic and skeletal tissues. In vitro developmental models currently rely upon costly and unreliable recombinant BMP proteins that do not enable dynamic or precise perturbation of the BMP signalling pathway. Here, we develop a novel optogenetic BMP signalling system (optoBMP) that enables rapid induction of the canonical BMP signalling pathway through illumination with blue light. We demonstrate the utility of the optoBMP system in multiple human cell lines to initiate signal transduction through phosphorylation and nuclear translocation of SMAD1/5, leading to upregulation of BMP target genes including Inhibitors of DNA binding ID2 and ID4. Furthermore, we demonstrate how the optoBMP system can be used to fine-tune activation of the BMP signalling pathway through variable light stimulation. Optogenetic control of BMP signalling will enable dynamic and high-throughput intervention across a variety of applications in cellular and developmental systems.

molecular biology↗

bioRxiv2020

microRNA-seq of cartilage reveals an over-abundance of miR-140-3p which contains functional isomiRs

MiR-140 is selectively expressed in cartilage. Deletion of the entire miR-140 locus in mice results in growth retardation and early-onset osteoarthritis-like pathology, however the relative contribution of miR-140-5p or miR-140-3p to the phenotype remains to be determined. An unbiased small RNA sequencing approach identified miR-140-3p as significantly more abundant (>10-fold) than miR-140-5p in human cartilage. Analysis of these data identified multiple miR-140-3p isomiRs differing from the miRBase annotation at both the 5 and 3 end, with >99% having one of two seed sequences (5 bases 2-8). Canonical (miR-140-3p.2) and shifted (miR-140-3p.1) seed isomiRs were overexpressed in chondrocytes and transcriptomics performed to identify targets. miR-140-3p.1 and miR-140-3p.2 significantly down-regulated 694 and 238 genes respectively, of which only 162 genes were commonly down-regulated. IsomiR targets were validated using 3 UTR luciferase assays. miR-140-3p.1 targets were enriched within up-regulated genes in rib chondrocytes of Mir140-null mice and within down-regulated genes during human chondrogenesis. Finally, through imputing the expression of miR-140 from the expression of the host gene WWP2 in 124 previously published datasets, an inverse correlation with miR-140-3p.1 predicted targets was identified. Together these data suggest the novel seed containing isomiR miR-140-3p.1 is more functional than original consensus miR-140-3p seed containing isomiR.

molecular biology↗

bioRxiv2018

Two Novel Forms of ERG Oscillation in Drosophila: Age and Activity Dependence

Over an animals lifespan, neuronal circuits and systems often decline in an inherently heterogeneous fashion. To compare the age-dependent progression of changes in visual behavior with alterations in retinal physiology, we examined phototaxis and electroretinograms (ERGs) in a wild-type D. melanogaster strain (Canton-S) across their lifespan. In aged flies (beyond 50% median lifespan), we found a marked decline in phototaxis, while motor coordination was less disrupted, as indicated by relatively stronger negative geotaxis. These aged flies displayed substantially reduced ERG transient amplitudes while the receptor potentials (RP) remained largely intact. Using a repetitive light flash protocol, we serendipitously discovered two forms of activity-dependent oscillation in the ERG waveforms of young flies: \"light-off and \"light-on\" oscillations. After repeated 500 ms light flashes, light-off oscillations appeared during the ERG off-transients (frequency: 50-120 Hz, amplitude: ~1 mV). Light-on oscillations (100-200 Hz, ~0.3 mV) were induced by a series of 50 ms flashes, and were evident during the ERG on-transients. Both forms of oscillation were observed in other strains of D. melanogaster(Oregon-R, Berlin), additional Drosophila species (funerbris, euronotus, hydei, americana), and were evoked by a variety of light sources. Both light-off and light-on oscillations were distinct from previously described ERG oscillations in visual mutants, such as rosA, in terms of location within the waveform and frequency. However, within rosA mutants, light-off oscillations, but not light-on oscillations could be recruited by the repetitive light flash protocol. Importantly though, we found that both forms of oscillation were rarely observed in aged flies. Although the physiological bases of these oscillations remain to be elucidated, they may provide important clues to age-related changes in neuronal excitability and synaptic transmission.

neuroscience↗