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Smith, W. V.

Publications and source records attributed to Smith, W. V..

8 recordsLinked to original sources

Forging Sustainable Research: Integrating Sustainability into Neuroscience Education

The health and wellbeing of living organisms and the environment are irrevocably interconnected. Animals constantly shape the environments in which they live, and environmental factors, in turn, shape the minds and behaviours of animals. The emerging discipline of environmental neuroscience studies this reciprocal interaction and offers a unique opportunity to integrate sustainability into undergraduate training. Here, we present and evaluate Forging Sustainable Research, an interdisciplinary undergraduate course that integrates teaching of neuroscience, biology, psychology, environmental science, and sustainable development. Students explore how research in these fields can be interlinked 24 and re-oriented towards addressing emerging environmental challenges. In parallel, students learn how to measure and mitigate the environmental impact of research activities. Student feedback suggests that the course is effective at raising awareness and understanding of sustainability in research, while also enhancing student perception of their own ability to promote positive change. As climate and ecosystem change impact all sectors, sustainability awareness in academic and professional spaces is increasingly sought after. Students in the course therefore receive training in transferable skills relevant for diverse career paths. In the long term, this course may serve as model for direct integration of sustainability training into undergraduate curricula in the natural sciences.

scientific communication and education↗

Promotion of Structured Motor Program Diversity Through Since-last-state Memory in Drosophila Larvae

Motor systems controlling locomotion must generate repetitive rhythmic activity, while also still retaining the ability to generate a diverse range of outputs. How motor systems monitor, regulate, and promote diversity of their own outputs is not well understood. Here, we perform single-step, variable-order and hidden-state Markov modelling (HSMM) on spontaneous fictive locomotor activity in the isolated Drosophila larval nervous system to examine how a motor system balances constraint and promotion of diversity amongst competing motor programs. We show that spontaneous fictive activity is structured by interacting mechanisms operating at multiple levels of sequence organisation. Analysis of one-step transition rules revealed a bias in activity towards activity states underlying exploration that in turn, promote transition to diverse outputs. In contrast, higher-order Markov, N-gram, and HSMM analysis indicated a memory biased towards revisiting recently executed motor programs. These mechanisms together suggest that the Drosophila larval locomotor system maintains a dynamic repertoire of possible motor outputs by monitoring recent activity and biasing future transitions accordingly. In this sense, fictive rhythmogenesis reflects a diversity-generating process: the larval locomotor network does not simply repeat a fixed motor programme or randomly transition from one state to another, but rather continually regulates access to rhythmic states based on recent experience. Together, these findings suggest that fictive locomotor dynamics are consistent with adaptive winner-takes-all competition between central pattern generating (CPG) modules that balance constraint and promotion of motor program diversity.

neuroscience↗

Optogenetic Control of Activity in Descending Tdc2+ Neurons Modulates Motor Program Bias in the Drosophila Larval Locomotor System

Motor systems must flexibly select between competing outputs while preserving stability of rhythmic outputs. In Drosophila larvae, the isolated central nervous system is capable of maintaining rhythmicity by generating multiple different fictive motor programs. The biogenic amines octopamine and tyramine are known to regulate larval locomotion, however, how the tdc2+ octopaminergic/tyraminergic system regulates motor program competition is not well understood. Here, we combine dual-colour calcium imaging and optogenetic manipulation to explore how tdc2+ neurons track, permit, and bias fictive motor activity in 3rd instar Drosophila larvae. We find that tdc2+ activity in the larval ventral nerve cord is strongly coupled to motor neuron activity across multiple fictive behaviours, indicating that the system is recruited broadly across the motor repertoire. Optogenetic depolarisation of tdc2+ neurons increases motor root bursting and induces a robust fictive forward bias, whereas optogenetic hyperpolarisation suppresses or abolishes fictive rhythms and generates a short-lasting, post-inhibitory rebound in fictive activity. Spatially-restricted stimulation reveals that posterior abdominal activation is especially effective at promoting fictive forward activity. Separating VNC-residing from brain-residing tdc2+ populations further shows that activation of descending brain-residing tdc2+ projections is sufficient to recapitulate this forward bias. Finally, tdc2+ activation induces short-lived post-stimulation changes in motor programme probability, including transient elevation of competing fictive backward instantaneous frequency. Together, these findings suggest that tdc2+ neurons act as a permissive and biasing modulatory layer within larval motor circuits, linking adrenergic-like signalling to motor programme competition.

neuroscience↗

WillCO2st: leveraging freely available real-time carbon forecasting for research sustainability reporting

Summary (Abstract)An increasing number of research institutions and funding bodies are making sustainability a focal point. The rapid rollout of auditing processes, such as the Laboratory Efficiency Assessment Framework (LEAF), and changing institutional policies, are creating demand for sustainability accounting upon researchers. Despite the increasing expectations on researchers to actively report their sustainability and demonstrate improvement, easy-to-use, and accurate reporting tools for electricity-associated emissions (scope 2) accounting are not widely available. Here, we created WillCO2st - a free program that enables fast, publication-read sustainability reports. WillCO2st makes use of real-time, region-specific conversion factor data freely available through resources like the Carbon Intensity and Electricity Maps API to create experimental carbon footprinting estimates using metadata from saved experimental files. Data can be simply click-and-dragged into WillCO2st to create an experimental sustainability audit within minutes. Further, we exemplified the utility of WillCO2sts live-nudging feature by quantifying the retrospective theoretical reduction in electricity-driven emissions from shifting experimental timing to times of day with lower carbon intensities. Overall, WillCO2st eases time and resource burden on researchers and serves as a model for how researchers can effectively and accurately engage with research sustainability auditing. Highlights WillCO2st is a free software platform that enables fast, publication-ready carbon emissions reporting for papers, grants, and internal audits. WillCO2st leverages various energy-to-emissions database to provide real-time, region-specific estimations of carbon intensity for the upcoming 48 hours, nudging users to switch to lower carbon times for research activities. WillCO2st integrates CodeCarbon to automatically audit Python-based coding scripts for experimental and computational-wide sustainability audits. Partial conformity (21%) to switching experimental time would have disproportionately produced a large carbon saving (50%) in our most recent publications experimental carbon footprint.

neuroscience↗

Octopamine and Tyramine Modulate Motor Program Competition in Drosophila larvae

Dynamic interactions amongst competing motor programs shape behavioural output. Here, we use bath application of biogenic amines octopamine (OA) and tyramine (TA) to explore operating principles of competition amongst central pattern generating (CPG) networks controlling locomotion in 3 rd instar Drosophila larvae. OA and TA share the same synthesis pathway and are contained in overlapping sets of neurons. Bath application of OA promoted fictive forwards locomotion, suppressed backwards locomotion, and induced bouts of fictive head sweeps during wash periods that were proportional to the promotion of forward waves. In contrast, TA, the conceptualised inhibitory antagonist to OA, promoted collisions and overlap of motor programmes, activity-dependent inhibition, and bouts of silence during wash periods. Co-application of OA and TA revealed bimodal state-dependent modulation with forward bias promotion exclusively if the pre-application network was not already forward dominant. Overall, our work provides insights into how adrenergic-like systems can modulate dynamics of motor competition among interacting CPGs within locomotor networks.

neuroscience↗

Doctoral Students as Carbon Accountants: Calculating Carbon Costs of a PhD in Neuroscience

Research is an energy and resource-demanding activity. However, despite increasing awareness and emerging sustainability initiatives, a paucity of data and methodological inconsistency continue to hamper effective and accountable emissions mitigation. With > 250,000 doctoral students graduating annually across all academic disciplines, empowering PhD students to engage in carbon accounting could provide a sizable and robust source of carbon data alongside a powerful generational force for decarbonisation. Here, we demonstrate how doctoral students and other researchers can consistently measure the carbon footprint of their work, using one PhD students research in a neuroscience Drosophila lab as our case study. We present a comprehensive life-cycle assessment of the equivalent carbon dioxide emissions (CO2e) generated by the students research activities, including measurement of scope 1 emissions associated with Drosophila husbandry; calculation of time- and region-specific scope 2 emissions produced by widely used techniques including calcium imaging, electrophysiology, and optogenetics; and estimation of scope 3 emissions associated with procurement and research-related travel. We found that research-related travel and procurement of laboratory supplies were responsible for the majority of annual emissions, up to 1942 kg CO2e and 543 kg CO2e respectively after accounting for aircraft radiative forcing. Using NESOs open-source Carbon Intensity API to account for temporal and geographical variation in the carbon intensity of UK National Grid energy, we found that persistent laboratory energy consumption released 10.99 kg CO2e, with an additional 3.56 kg CO2e scope 2 and 3.6 kg CO2e scope 1 emissions underpinning direct research activities. Finally, we discuss the challenges of accurately carbon foot printing research across disciplines in the UK and beyond, highlighting the value of regionally precise open-source energy mix data and the need for data openness within research supply chains. Overall, we present a common framework for including carbon footprint analyses as Carbon Appendices to PhD theses to generate carbon footprint data across disciplines. Beyond the benefits of such data for informed emissions mitigation, we envision doctoral students carrying insights from carbon appendices forward into academia and industry to catalyse a community-driven decarbonisation of the research sector.

neuroscience↗

Generation of motor program diversity and variability through inhibitory circuit motifs in the Drosophila larval locomotor system

How do neural networks generate and regulate diversity and variability in motor outputs with finite cellular components? Here we examine this problem by exploring the role that inhibitory neuron motifs play in generating mixtures of motor programs in the segmentally organised Drosophila larval locomotor system. We developed a computational model that is constrained by experimental calcium imaging data. The model comprises single-compartment cells with a single voltage-gated calcium current, which are interconnected by graded excitatory and inhibitory synapses. Local excitatory and inhibitory neurons form conditional oscillators in each hemisegment. Surrounding architecture reflects key aspects of inter- and intrasegmental connectivity motifs identified in the literature. The model generates metachronal waves of activity that recapitulate key features of fictive forwards and backwards locomotion, as well as bilaterally asymmetric activity in anterior regions that represents fictive head sweeps. The statistics of inputs to competing command-like motifs, coupled with inhibitory motifs that detect activity across multiple segments generate network states that promote diversity in motor outputs, while at the same time preventing maladaptive overlap in motor programs. Overall, the model generates testable predictions for connectomics and physiological studies while providing a platform for uncovering how inhibitory circuit motifs underpin generation of diversity and variability in motor systems.

neuroscience↗

Selective Vulnerability of Tripartite Synapses in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder. Separate lines of evidence suggest that synapses and astrocytes play a role in the pathological mechanisms underlying ALS. Given that astrocytes make specialised contacts with some synapses, called tripartite synapses, we hypothesise that tripartite synapses could act as the fulcrum of disease in ALS. To test this hypothesis, we have performed an extensive microscopy-based investigation of synapses and tripartite synapses in the spinal cord of ALS model mice and post-mortem human tissue from ALS cases. We reveal widescale synaptic changes at the early symptomatic stages of the SOD1G93a mouse model. Super-resolution microscopy reveals that large complex postsynaptic structures are lost in ALS mice. Most surprisingly, tripartite synapses are selectively lost while non-tripartite synapses remain in equal number to healthy controls. Finally, we also observe a similar selective loss of tripartite synapses in human post-mortem ALS spinal cords. From these data we conclude that tripartite synaptopathy is a key hallmark of ALS.

neuroscience↗