Biology subjects

Simon, A. F.

Publications and source records attributed to Simon, A. F..

8 recordsLinked to original sources

bioRxiv2026

A novel function of neuroligin 3: Beyond sociality, Regulating lifespan in Drosophila

Neuroligins are conserved postsynaptic adhesion proteins involved in synaptic function and behaviour. In Drosophila melanogaster, Neuroligin 3 (Nlg3) regulates social behaviour, sleep and synaptic architecture. We now report, through analysis of publicly available transcriptomics data, confirmed with RT-qPCR data, that loss-of-function of the nlg3 gene downregulates the expression of longevity-associated genes foxo, hsp70s, and hsp68. Graded genetic manipulation of the Drosophila melanogaster neuroligin 3 (nlg3) gene indeed modulates both social spacing and lifespan. Specifically, reduced nlg3 expression (via heterozygous deletion, or transposable-element insertion) extends lifespan in both sexes, while overexpression or complete deletion shortens it. In contrast, overexpression or complete loss of nlg3 leads the flies to be further apart (increased social distance, or social space), as does RNAi knockdown, while heterozygous reduction of nlg3 expression either lowers or does not alter the flies social space. This work identifies a previously unrecognized link between a conserved synaptic gene, social behaviour, and organismal longevity.

neuroscience↗

bioRxiv2026

Context-dependent modulation of social space by dopamine receptors in the Drosophila melanogaster mushroom body

Social behavior takes many forms, yet the fundamental principles of social circuit function are thought to be evolutionarily conserved. Foundational behaviors that precede more complex interactions can reveal the mechanisms underlying these circuits. Social spacing, the regulation of preferred inter-individual distances, is one such behavior and can be quantified in the genetically tractable model Drosophila melanogaster. Dopamine and the mushroom body brain region regulate spacing in Drosophila, and extensive dopaminergic signaling occurs within this structure, but receptor-level contributions remain unclear. This report examines how the four dopamine receptors (DopEcR, Dop1R1, Dop1R2, Dop2R) mediate mushroom body-targeted dopaminergic signaling during spacing. Manipulating receptor expression in the entire mushroom body or specific lobes revealed spacing effects that depended on genetic background, receptor identity, sex, and lobe. Receptors could be organized into two opposing pairs: DopEcR and Dop1R1 manipulations increased inter-individual distance, whereas Dop1R2 and Dop2R manipulations decreased inter-individual distance. However, each receptor produced a distinct pattern of effects when male and female data were analyzed across all three mushroom body lobes. These findings support a model in which distributed dopaminergic input engages all four receptors to shape context-dependent spacing decisions, offering insight into social circuit organization in Drosophila and beyond. Article SummaryThis study examined how dopamine receptors in the mushroom body (MB) of Drosophila melanogaster regulate social spacing, the distance between individuals in groups. The expression of four dopamine receptors was manipulated in different MB lobes to identify their contributions to spacing behavior. The receptors showed distinct effects that depended on receptor type, sex, and MB region. Two receptors increased spacing between flies, while two decreased spacing. These findings support a circuit model in which distributed dopaminergic signals are differentially weighted to generate context-dependent spacing decisions. This work may provide insight into regulation of social spacing in other organisms.

neuroscience↗

bioRxiv2025

Deciphering the circular RNAs landscape in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, with most cases lacking a clear genetic basis. Emerging evidence highlights the involvement of non-coding RNAs, particularly circular RNAs (circRNAs), in disease onset and progression. In this study, we investigated circRNAs implicated in ALS and related motor neuron diseases (MNDs). First, we conducted a systematic review to identify ALS-associated circRNAs, followed by in silico analyses of 15 selected candidates. Our results revealed that hsa_circ_0000099, hsa_circ_0001017, hsa_circ_004846, and hsa_circ_0034880 regulate a high number of ALS-related genes through miRNA sponging. Pathway enrichment analysis indicated that hsa_circ_0000099 is particularly involved in unfolded protein response, oxidative stress, cell cycle regulation, and apoptosis. Protein-RNA interaction analysis further showed that ALS-related circRNAs can sponge 20 RNA-binding proteins, with FMR1, ELAVL1, EIF4A3, and SRSF1 exhibiting the highest number of interactions. Additionally, molecular docking analysis demonstrated that FUS mutations significantly alter its binding affinity to hsa_circ_0000567 and hsa_circ_0060762. RNA-seq data from ALS patients confirmed significant alterations in the expression of host genes of ALS-related circRNAs and hub proteins across affected tissues, including the spinal cord and multiple brain regions. Collectively, these findings support circRNAs as active contributors to ALS pathogenesis. In particular, the host gene of hsa_circ_0000099, which is expressed in the spinal cord and hippocampus, emerges as a potential biomarker for tissue-specific impairment in ALS. Moreover, its regulatory role in key ALS-related cellular pathways underscores its promise as a candidate for biomarker development and therapeutic targeting. Further experimental validation is warranted to confirm its role in ALS pathology. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/677871v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@15d0389org.highwire.dtl.DTLVardef@1934327org.highwire.dtl.DTLVardef@11ddd3aorg.highwire.dtl.DTLVardef@1a74c09_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Neuroligin 3 highlights sexually dimorphic circuitry in Drosophila social spacing

In Drosophila melanogaster, the autism-related Neuroligin 3 (Nlg3) protein is a postsynaptic membrane protein important for synapse development and regulation, which plays a role in social spacing behaviour. Here, we report the localization of Nlg3 to the calyx of the mushroom bodies (MB), optic lobes (OL), and protocerebral bridge (PB). Using RNA interference, nlg3 knockdown in each of these structures recapitulated the effect of knocking down it in all nlg-3 neurons. Hyperactivation and silencing of these neurons in the MB, but not the PB, controls social space in males and females, while hyperactivating and silencing of all nlg3-expressing neurons, including within the MB, PB, and OL, regulates male and female social space. Knocking down neurotransmitter biosynthesis enzymes, which decreases the amount of neurotransmitter release, showed that reducing acetylcholine release from the MB decreased female social space, whereas knocking down any dopamine receptor in the MB increased male social space. Lastly, to investigate the sexually dimorphic effects on social spacing previously seen in nlg3 mutants, we examined a subset of sexually dimorphic fruitless-expressing (fru)P1 neurons known to regulate sexually dimorphic behaviours. Hyperactivation of those fruP1 neurons decreased social space in both sexes, while silencing those fruP1 neurons specifically increased male social space without affecting females. Our findings highlight a sex-specific social space neural circuitry that includes the OL, MB, and fruP1 neurons, while uncovering the underlying basis of some of the sex differences in this behaviour. Article SummaryIn vinegar flies (Drosophila melanogaster), the autism-related Neuroligin 3 protein (Nlg3) controls neuronal development and regulation but also affects fly social behaviour. Nlg3 is localized to the mushroom bodies (MB), protocerebral bridge, and the optic lobes. We show that those structures are important in determining social space in a sex dependant manner. In addition, reducing acetylcholine release from the MB affects female social space, while reducing dopamine receptors of the MB only affect male behaviour. Finally, the fruitless sexually dimorphic neurons control social behavior differently in males and females.

animal behavior and cognition↗

bioRxiv2024

Impact of the COVID-19 Pandemic on Undergraduate Research in the Department of Biology at Western University: Effect on project types, learning outcomes, and student perceptions.

Undergraduate research is a high impact practice that offers numerous benefits to students, academic institutions, and the wider scientific community. Unfortunately, undergraduate research has faced restrictions due to the COVID-19 pandemic. This study aimed to assess how the COVID-19 pandemic has impacted: (1) the number and types of undergraduate research projects performed in the Department of Biology at the University of Western Ontario, and (2) the satisfaction-levels and perceived learning outcomes of students performing these projects. This study also aimed to incorporate a One Health framework through an emphasis on stakeholder involvement and the need for future action. A survey of 33 students who completed an undergraduate research project in the Department of Biology in the 2020/2021 academic year, and 68 students who completed an undergraduate research project in the 5 years prior was conducted. In keeping with the One Health approach, key stakeholders were identified, and a stakeholder map was constructed. The number of projects performed did not change dramatically despite COVID-19 restrictions. However, a shift towards dry research was observed with 87.9% of students in the 2020/2021 academic year conducting dry research, compared to 16.4% of students in the 5 years prior. Students who conducted research in the 2020/2021 academic year indicated lower overall levels of satisfaction and enjoyment, though their perceived learning outcomes were consistent with students who completed their projects in the 5 years prior. 53 key stakeholders from academia, government, industry, media, and the public were identified. Students provided invaluable feedback on their undergraduate research experiences that can be used to improve the quality of undergraduate research courses in the Department of Biology in the future. Findings may be of use to other departments and educational institutions that are seeking to improve their own undergraduate research courses amidst the COVID-19 pandemic or looking to incorporate experiential-based learning techniques into existing online courses.

scientific communication and education↗

bioRxiv2023

Recovery from social isolation requires dopamine in males, but not the autism-related gene nlg3 in either sex

Social isolation causes profound changes in social behaviour in a variety of species including humans, monkeys, mice, bees, and vinegar flies. However, the genetic and molecular mechanisms modulating behavioural responses to both social isolation and social recovery remain to be elucidated. In this study, we quantified the behavioural response of vinegar flies to social isolation through the use of two distinct protocols, one involving flies social space preference and the other assessing flies sociability, defined as their spontaneous tendencies to form groups. We found that social isolation increased social space and reduced sociability. These effects of social isolation, however, were reversible and could be reduced after 3 days of group housing. Flies with a loss of function of neuroligin3 (ortholog of autism-related neuroligin genes) with known increased social space in a socially enriched environment, were still able to recover from social isolation. Using a UAS-TH-RNAi driven in all neurons, we show that dopamine is important for a response to social isolation and recovery in males but not in females. Furthermore, only in males, dopamine levels are reduced after isolation and are not recovered after group housing. Finally, in socially enriched flies with a loss of function of neuroligin3, dopamine levels are reduced in males, but not in females. We propose a model to explain how dopamine and neuroligin3 are involved in the behavioural response to social isolation and its recovery in a dynamic and sex-specific manner.

neuroscience↗

bioRxiv2022

Aging and memory are altered by genetically manipulating lactate dehydrogenase in the neurons or glia of flies

The astrocyte-neuron lactate shuttle hypothesis posits that glial-generated lactate is transported to neurons to fuel metabolic processes required for long-term memory. Although studies in vertebrates have revealed that lactate shuttling is important for cognitive function, it is uncertain if this form of metabolic coupling is conserved in invertebrates or is influenced by age. Lactate dehydrogenase (Ldh) is a rate limiting enzyme that interconverts lactate and pyruvate. Here we genetically manipulated expression of Drosophila melanogaster lactate dehydrogenase (dLdh) in neurons or glia to assess the impact of altered lactate metabolism on invertebrate aging and long-term courtship memory at different ages. We also assessed survival, negative geotaxis, brain neutral lipids (the core component of lipid droplets) and brain metabolites. Both upregulation and downregulation of dLdh in neurons resulted in decreased survival and memory impairment with age. Glial downregulation of dLdh expression caused age-related memory impairment without altering survival, while upregulated glial dLdh expression lowered survival without disrupting memory. Both neuronal and glial dLdh upregulation increased neutral lipid accumulation. We provide evidence that altered lactate metabolism with age affects the tricarboxylic acid (TCA) cycle, 2-hydroxyglutarate (2HG), and neutral lipid accumulation. Collectively, our findings indicate that the direct alteration of lactate metabolism in either glia or neurons affects memory and survival but only in an age-dependent manner. Author SummaryThe brain is composed of metabolically demanding cell types that must remain functional throughout life to maintain cognitive tasks like memory formation. How brain metabolism varies between cell-types across the lifespan is uncertain. It has been suggested that in vertebrate brains glia breakdown sugars to produce lactate and shuttle it to neurons to support long-term memory and survival. Yet, this phenomenon has not been directly tested in invertebrates. In Drosophila melanogaster flies, we genetically manipulated lactate dehydrogenase, a central enzyme in lactate metabolism, specifically within the adult brain. We discovered that shifting lactate metabolism to either higher or lower levels in neurons caused decreased survival and worse long-term memory with age. In contrast, we found increased glial lactate metabolism worsened survival, whereas decreased glial lactate metabolism impaired long-term memory in aged flies. Both increased glial or neuronal lactate metabolism led to increased accumulation of metabolites, such as 2-hydroxyglutarate, mitochondrial metabolites, and neutral lipids, in aged fly brains. These findings provide evidence for the first time in invertebrates that lactate and memory are connected and altered lactate metabolism in neurons and glia differentially impact survival and memory, but only in an age-dependent manner. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/512981v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@6b34d7org.highwire.dtl.DTLVardef@5a159forg.highwire.dtl.DTLVardef@41a3f6org.highwire.dtl.DTLVardef@17377ea_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

Is Drosophila melanogaster Stress Odorant (dSO) really an alarm pheromone?

Social interactions are crucial for the reproduction and survival of many organisms, including those using visual, auditory and olfactory cues to signal the presence of danger. Drosophila melanogaster emits an olfactory alarm signal, termed the Drosophila stress odorant (dSO) in response to mechanical agitation or electric shock, and conspecifics avoid areas previously occupied by stressed individuals. However, the contextual, genetic and neural underpinnings of the emission of, and response to dSO, have received little attention. Using a binary choice assay, we determined that neither age and sex of emitters, nor the time of the day, affected the emission or avoidance of dSO. However, both sex and mating status affected the response to dSO. We also demonstrated that dSO was not species specific so it should not be considered a pheromone but a general alarm signal for Drosophila. However, the response levels to both intra and inter-specific cues differed between species and possible reasons for these differences are discussed. HIGHLIGHTSO_LIEmission of dSO, a highly volatile chemical blend emitted by stressed flies, is not context specific C_LIO_LIResponse to dSO is context specific, affected by factors such as age and mating status. C_LIO_LIAs flies respond to volatiles for stressed heterospecifics, dSO should not be considered an alarm pheromone, but as an alarm cue. C_LI

animal behavior and cognition↗