Posters presented at SNG 2026

Poster 1: Sai Parepalli (University of Edinburgh): Deprescribing cardiovascular medications in adults with dementia: evidence from target trial emulation and cumulative exposure modelling

There is uncertainty about cardiovascular drug effects in adults with dementia. We estimated causal effects associated with deprescribing cardiovascular medication in people with dementia.

We emulated a target trial (TTE) and fit a cumulative exposure (CE) model using Scottish EHRs (2007–2021). 122,070 people with dementia >50yrs on ≥1 year of antihypertensives, statins, or antiplatelets were identified. Outcomes were all-cause mortality and major adverse cardiovascular events. Cox and competing risks regression models estimated adjusted hazard ratios for intention-to-treat, per additional year deprescribed, and by subsequent time deprescribed.

Deprescribing was associated with higher aHRs of mortality across medications (Antihypertensives: TTE aHR 1.19 [95%CI: 1.17-1.22], CE aHR 1.04 [95%CI: 1.04-1.05]; Antiplatelets: TTE aHR 1.14 [1.12-1.16], CE aHR 1.02 [1.01-1.03]; Statins: TTE aHR 1.24 [1.22-1.27], CE 1.09 [1.08-1.10]). For MACE outcomes, the association was around null (Antihypertensives: TTE aHR 0.95 [95% CI: 0.92-0.98], CE aHR 0.99 [0.98-1.01]; Antiplatelets: TTE aHR 0.95 [0.92-0.99], CE aHR 0.99 [0.97-1.01]; Statins: TTE aHR 0.97 [0.93-1.00], CE 1.03 [1.02-1.05]).

Deprescribing cardiovascular medications was associated with: 1) an overall higher risk of all-cause mortality, likely reflecting the deprescribing decision context, and 2) no increased risk of MACE.

Poster 2: Natalie Ling Sum Hung (University of Edinburgh): Distinct spectral, connectivity, and firing dynamics around absence seizures in rat models of SYNGAP1 and GRIN2B neurodevelopmental disorders

There is uncertainty about cardiovascular drug effects in adults with dementia. We estimated causal effects associated with deprescribing cardiovascular medication in people with dementia.

Deprescribing cardiovascular medications was associated with: 1) an overall higher risk of all-cause mortality, likely reflecting the deprescribing decision context, and 2) no increased risk of MACE.

Poster 3. Paige Windmill (University of Edinburgh): Heterogeneity of locus coeruleus prediction error responses

Prediction errors occur when an individual’s prediction of the environment differs from real-world occurrence and are important neuronal signals for driving learning. In the activity of the locus coeruleus (LC), a key neuromodulatory centre for driving learning, responses consistent with prediction errors have been observed following a variety of stimuli. The learning-dependence and heterogeneity of LC prediction error signaling is, however, not well established. To explore this, we recorded LC calcium activity using fibre photometry while mice learned a spatial reward task in virtual reality. During performance, we presented perturbations designed to evoke different prediction errors, including rewards in unexpected locations, and unexpected halts in the motion of the environment (visuomotor mismatches). We find significant variation in LC responses across mice: some imaging sites show large calcium responses to visuomotor mismatches, while others show large responses to rewards and selective ramping of activity toward expected reward locations. These differential responses develop with improved performance in the task, in a manner that suggests that they reflect learned reward value profiles. The results indicate that reward prediction error is a major component of LC output, and point to heterogenous LC neurons with different reward prediction error signaling functions.

Poster 4: Siobhan Adesida (University of Glasgow): A Humanized Tri-culture of Sensory Neurons, Macrophages and Schwann Cells to Explore Neuropathic Pain Mechanisms

Backgrounds & Aims:

Animal models have facilitated major advances in pain research; to best translate these findings to clinical treatments we need strong translational models. In the peripheral nervous system, growing evidence implicates non-neuronal cells, particularly macrophages and Schwann cells, interacting with sensory neurons in neuropathic pain. Despite this, the cellular and molecular mechanisms driving this crosstalk remain poorly understood. This project aims to address this gap by developing a human- iPSC tri-culture model comprising the three cell types to study healthy state and environmental injury-induced interactions and identify novel therapeutic targets.

Methods:

Human iPSCs are differentiated in parallel into sensory neurons (iSNs), Schwann cells (iSCs), and macrophages (iMacs) and assembled into co-culture and tri-culture systems. Localized neuronal injury is induced using laser ablation, enabling precise and reproducible modelling of nerve damage. Cellular responses to injury are assessed using live-cell calcium imaging and gene expression analyses to quantify changes in neuronal excitability and inflammatory signalling, providing mechanistic insight into neuron–immune interactions associated with neuropathic pain.

Results:

We have successfully generated iSNs, iSCs, and iMacs with expected phenotypic characteristics and gene expression profiles. iSNs express BRN3A and extend extensive neurite networks, while iMacs express IBA1 and are competent phagocytes. iSCs express S100β and align closely with iSN processes. Short-term tri-culture viability has been established, with ongoing refinement to improve long-term stability. Laser ablation produces controlled, localized neurite injury and we have investigated its impact in co- and tri-culture systems. We further present the development of medium-throughput assays of neuronal excitability using AAV-delivery of GCaMP8s combined with live-cell fluorescence imaging.

Conclusion:

Integrating iPSC-derived cells into a tri-culture injury model provides a novel platform to study neuropathic pain mechanisms in a human-relevant context. This approach bridges the translational gap between preclinical studies and clinical applications.

Poster 5: Jack Webster (University of Edinburgh): Altered axonal initial segment development links circuit-level and Kv7 potassium channel dysfunction in an Fmr1 knockout rat

Fragile X syndrome (FXS) is the leading monogenetic cause of intellectual disability and autism, yet how basic hippocampal circuit properties evolve across development for this condition remains unclear. To address this gap, we studied CA1 pyramidal neurons in male Fmr1 knockout rats at P12–15 and 6–10 weeks using ex vivo electrophysiology, pharmacology, imaging and biochemistry. P12–15 knockout neurons showed impaired sustained firing, progressive action potential broadening and enhanced activity-dependent synaptic vesicle replenishment. These defects were entirely normalised by 6–10 weeks. These phenotypes were linked to dysfunction of axon initial segment (AIS) anchored-Kv7 potassium channels, as Kv7 activation altered action potential dynamics and neurotransmission in WT but not Fmr1 KO neurons. Rather than directly altering Kv7 channel function, Fmr1 knockout altered AIS development such that Kv7 became functionally inert. These findings suggest that altered AIS developmental trajectory drives early, transient Kv7-dependent CA1 dysfunction in FXS and highlight how alterations in AIS development can have profound functional impacts.

Poster 6: Ridvan Kucuk (University of Strathclyde): Pluripotency validation and neuronal differentiation of human iPSCs for a stroke-on-a-chip model

Stroke arises from an acute loss of cerebral perfusion, precipitating rapid neuronal injury and irreversible tissue damage. Despite its substantial global burden, effective therapies remain limited. Interventions successful in rodents tend to fail in human trials, highlighting the need for more predictive human relevant models. Our aim is to validate the pluripotency of human induced pluripotent stem cell (hiPSC) lines that will be differentiated into neurons and utilised in a stroke-on-a-chip model to study stroke mechanisms.

The pluripotency of three hiPSC lines from separate donors was validated using flow cytometry and quantitative PCR (qPCR) to detect markers of pluripotency, prior to being differentiated via dual SMAD inhibition.

The flow cytometry experiments revealed that >90% of the cells expressed SSEA-4, TRA-1-60 and TRA-1-81, while the qPCR detected the expression of OCT4, SOX2 and NANOG in all three cell lines. Qualitative data indicated differentiation into neural progenitor cells (NPCs) and terminal differentiation into neurons for one of the three lines.

Overall, our experiments verified the expression of pluripotency surface markers and key transcription factors regulating pluripotency and initial results indicate differentiation into NPCs and neurons laying the foundations for further experiments working towards the stroke-on-a-chip model.

Poster 7: Trinity Rungasamy (University of Edinburgh): Using iPSC and organoid models to investigate MAPT expression and dysfunction in oligodendrocytes

Frontotemporal dementia (FTD) is the most common cause of early-onset dementia, with 10–20% of cases caused by mutations in the microtubule-associated protein tau (MAPT) gene. While tau pathology is well characterised in neurons, the contribution of oligodendrocyte dysfunction to disease progression remains poorly understood despite evidence of impaired oligodendrocyte function and reduced myelin integrity in MAPT-associated FTD. This study aims to investigate the role of MAPT expression in oligodendrocytes using human induced pluripotent stem cell (iPSC) and organoid models. iPSC-derived oligodendrocytes carrying the MAPT S305N mutation were differentiated and assessed for tau expression and maturation. Preliminary findings demonstrate tau expression in both oligodendrocyte precursor cells and maturing oligodendrocytes and suggest increased tau expression in MAPT-mutant oligodendrocytes. In parallel, to investigate cell–cell interactions in a more physiologically relevant environment, GFP-labelled oligodendrocyte precursor cells were injected into cortical iPSC-derived organoids. Injected cells successfully integrated throughout the organoid, associated closely with neurons and matured into MBP-positive oligodendrocytes expressing mature lineage markers within eight weeks. Ongoing work will utilise MAPT knockdown in oligodendrocyte precursor cells prior to organoid injection to investigate the cell-autonomous and non-cell-autonomous roles of MAPT using our novel oligodendrocyte-infiltrated organoid model.

Poster 8: Simon Achi Omerigwe (University of Strathclyde): Developing Human iPSC-Derived Cerebral Organoids for Stroke Modelling: Multi-Level Quality Validation

Introduction: Human induced pluripotent stem cell (hiPSC)-derived cerebral organoids have emerged as promising human-based three-dimensional models for investigating neurological diseases and accelerating therapeutic discovery. However, robust quality validation is essential before their application in disease modelling and drug screening. This study aimed to establish and validate a reproducible hiPSC-derived cerebral organoid platform for future therapeutic candidate profiling in ischaemic stroke.

Materials and Methods: Human iPSCs were first assessed for pluripotency using flow cytometry for the surface markers SSEA-4, TRA-1-60 and TRA-1-81, alongside RT-qPCR analysis of the pluripotency genes OCT4, SOX2 and NANOG. Following directed differentiation, cerebral organoids were evaluated for quality control measures through linear growth curve analysis and functional calcium imaging. RT-qPCR will be deployed to further confirm cortical specification and neuronal maturation through expression of dorsal forebrain and neuronal markers (PAX6, FOXG1, EMX2, TBR1), while non-cortical lineage markers (GSX2, NKX2.1, COL1A2) will determine high differentiation specificity.

Results: Flow cytometry, brightfield imaging and linear growth analysis demonstrated reproducible organoid development over time. Preliminary functional calcium imaging further demonstrated neuronal and astrocytic activities, supporting the establishment of a supposed active neuronal network.

Conclusions: Collectively, these preliminary findings support the establishment of a human cerebral organoid platform with potential for ischaemic stroke modelling. Ongoing validation through oxygen-glucose deprivation and therapeutic testing will further assess its reproducibility and translational potential.

Poster 9: Charlotte Wu (University of Edinburgh): Microglia absence on behavioural phenotypes and cognitive functions in a genetic model of Alzheimer’s disease

The brain's resident immune cells, microglia, have been closely linked with neuropathology in Alzheimer's disease (AD). Their role in cognitive functions in prodromal AD is, however, not fully elucidated. We ask whether and what type of cognitive functions are dependent on microglia at an early phase of beta-amyloid deposition. We cross mice lacking microglia (Csf1r∆FIRE/∆FIRE) and mice with risk genes of AD. Offspring from the selected strain are healthy and fertile. We find that adult mice without microglial show normal movement, working memory, object or location recognition memory, and spatial or reversal learning rates. Impairment in contextual fear memory is observed in AD mice, but not in AD mice without microglia. Collectively, microglia absence does not affect a wide range of behavioural and cognitive functions and can prevent specific memory impairment in AD.

Poster 10: Wei Huang (University of Edinburgh): Deciphering the molecular heterogeneity of motor neuron synapses in vivo

Synapses are highly diverse structures in terms of structural organization, molecular composition, and function. Synaptic heterogeneity underlies the capacity of neural circuits for flexible computation and adaptive plasticity. Although synaptic heterogeneity has long been recognized as functionally important, it remains poorly understood which mechanisms underlie its expression and whether it is developmentally. A major unresolved challenge is linking different physiological phenotypes to structural and molecular diversity at synapses during development. The SNARE proteins, resides at the presynaptic sides, constitute a large family that are responsible for nearly all fusion events involved in the secretory pathway. In my project, I will focus on the v-SNARE protein VAMP1 and VAMP2, essential components of the neurotransmitter release machinery, as a case study to address this question. Our lab generated in vivo reporters of endogenous VAMP1 and VAMP2 using CRISPR/Cas9-based knock-in. We discovered that individual motor axon synaptic boutons can display heterogeneous Vamp1/2 composition, with some boutons positive for only VAMP1, only VAMP2, or both. However, it is unclear how such heterogeneity emerges in individual axons and whether it contributes to variability in synaptic strength and output. In my project, I will use zebrafish as a model organism, to investigate (1) the emergence of VAMP heterogeneity at the NMJs; (2) how VAMP heterogeneity relates to functional heterogeneity along motor neuron synapses; and (3) how NMJ is affected in zebrafish carrying human VAMP1/2 mutations.

Poster 11: Lauramariu Schino (University of Glasgow): Co-culture of Human iPSCs-Derived Cells Enables Study Of Macrophage Sensitization Of Injured Neurons

Background and Aims: Neuroimmune interactions between macrophages and sensory neurons are key drivers of neuropathic pain (NeuP), yet therapies targeting these pathways have shown limited clinical success. We have developed a fully human induced pluripotent stem cell (iPSC)-derived co-culture model of sensory neurons (iSNs) and macrophages (iMacs) to investigate the mechanisms underlying neuronal sensitisation following injury. This platform aims to identify macrophage-derived mediators that drive pathological neuroimmune signalling and support the development of more effective analgesic therapies.

Methods: Mature iSNs and iMacs were co-cultured and characterised by immunohistochemistry using established neuronal and macrophage markers. Mechanical injury was applied to model neuronal damage. Sensory neurons were fluorescently labelled using adeno-associated viral (AAV) reporters, enabling injury-free purification by fluorescence-activated cell sorting (FACS). Genetically encoded Ca²⁺ indicators and activity-dependent fluorescent reporter systems were introduced to assess neuronal excitability.

Results: A robust and reproducible human co-culture system was established, demonstrating expected phenotypic characteristics of both cell types. We optimised injury-free fluorescent labelling, FACS-based isolation of sensory neurons, and protocols for characterising transcriptional responses following injury. In addition, medium-throughput assays of neuronal excitability, including Ca²⁺ imaging and fluorescent reporter systems, were successfully implemented.

Conclusions: This human co-culture platform enables mechanistic investigation of macrophage-mediated neuronal sensitisation and provides a translationally relevant system for identifying therapeutic targets and evaluating candidate analgesics for neuropathic pain.

Poster 12: Amy Dunne Miller (University of Dundee): Elucidating the role of secreted kinase Fam20C in microglia

Secreted kinase FAM20C is an atypical kinase which phosphorylates the majority of the phospho-secretome. This kinase is involved in skeletal development, bone mineralisation, nutrition, and calcium signalling via phosphorylation of secreted proteins. Even though 80% of the cerebral spinal fluid components are phosphorylated at the FAM20C consensus motif, SxE/pS, the role of FAM20C in the central nervous system is unknown. Microglia have extensive roles in the adult CNS and the developing brain, many of which rely heavily on the secretory factors. Furthermore, microglia and macrophages express high levels of FAM20C, however the role of this kinase in these cells has not been explored. In this work I identify key regulators of FAM20C expression in microglia. By establishing a FAM20C KO microglial line I describe the role of FAM20C in response to an inflammatory stimulus, LPS, and to TGF-β. Furthermore, with the use of primary microglia and immortalised cell lines, I demonstrate that FAM20C is involved in phagocytosis and migration of myeloid cells.

Poster 13: Danial Kordbacheh (University of Dundee): Design, Development, Validation, and Application of a Novel In Vitro Therapeutic Ultrasound Platform with Integrated Real-Time Optical Monitoring for Sonodynamic Therapy

Sonodynamic therapy (SDT) is an emerging non-invasive treatment modality that combines low-intensity therapeutic ultrasound with sonosensitising agents to selectively induce tumour cell death. Despite its considerable potential, progress in SDT research has been limited by the lack of standardised in vitro platforms capable of delivering reproducible ultrasound exposure while simultaneously monitoring treatment effects in real time.

This PhD project presents the design, development, validation, and application of a novel in vitro therapeutic ultrasound platform integrating real-time optical monitoring for SDT investigations. The platform has been engineered to provide controlled and repeatable ultrasound delivery while enabling continuous visual observation of biological and material responses during exposure. The system incorporates precise acoustic alignment, compatible cell culture components, and an integrated optical imaging approach to improve experimental reproducibility and facilitate quantitative assessment of treatment outcomes.

Validation of the platform includes acoustic characterisation, optimisation of exposure conditions, and evaluation of system performance for therapeutic ultrasound applications. The platform is subsequently applied to investigate sonodynamic therapy protocols, providing a robust experimental environment for future studies on ultrasound-mediated cancer treatment. By improving experimental standardisation and real-time observation capabilities, this platform represents an important step towards more reliable preclinical SDT research and supports the translation of therapeutic ultrasound technologies into biomedical applications.

Poster 14: Ana Jurado Santos (University of Glasgow): Selective Targeting and Chemogenetic Silencing of Injured Sensory Neurons for Neuropathic Pain

Neuropathic pain remains challenging to treat because current approaches suppress neuronal activity indiscriminately, risking loss of normal sensory function. We hypothesised that injured primary afferents are key drivers of ongoing neuropathic pain and that selective targeting of these neurons could provide a therapeutic strategy.

Using single-cell ATAC-sequencing of naïve and axotomised sensory neurons, we identified an injury-responsive regulatory element that exhibits selective chromatin accessibility following peripheral nerve injury. To assess its targeting specificity, it was incorporated into an AAV reporter construct driving GFP expression. Following spared nerve injury (SNI), GFP expression was largely restricted to injured sensory neurons, with minimal expression in uninjured counterparts. Reporter expression was observed across a broad range of neuronal sizes, suggesting targeting is not restricted to specific sensory neuron subtypes.

To explore therapeutic potential, GFP was replaced with the humanised chemogenetic silencer PSAM4-GlyR. This receptor can be selectively activated by varenicline, producing shunting chloride currents that suppress neuronal activity. Preliminary histological analysis of this PSAM4-GlyR-mCherry construct demonstrates successful expression within injured sensory neurons. Ongoing studies are evaluating whether selective silencing of injury-targeted afferents reduces pain behaviours following SNI.

Poster 15: Abbey Begen (University of Glasgow): Mapping Muscarinic Circuits: Unravelling mAChR1 and mAChR4 Expression and Connectivity in the Brain

Understanding how muscarinic acetylcholine receptors (mAChRs) are distributed and function in the brain is key to advancing our knowledge of cholinergic signalling in both healthy and pathological states. Among the five subtypes, mAChR1 and mAChR4 stand out as promising therapeutic targets because they can influence dopaminergic, cholinergic, and glutamatergic pathways. Disruptions in these receptors are linked to neuropsychiatric disorders like schizophrenia and Alzheimer's, underscoring their potential for developing receptor-specific treatments. To define the cellular and circuit-level organisation of mAChR1 and mAChR4, immunohistochemistry, adeno-associated virus (AAV) tracing, and advanced imaging approaches are combined with novel Cre-loxP mouse models in which receptor-expressing cells are fluorescently labelled with GFP. This strategy enables precise identification and characterisation of receptor-expressing populations and their connectivity. Recent results show that mAChR1 and mAChR4 are expressed in distinct neuronal populations within the hippocampus and lateral septum, regions heavily involved in neurodegeneration, cognition, and neuropsychiatric disorders. Furthermore, mAChR4 neurons in the lateral septum project to the hypothalamus and ventral tegmental area (VTA), revealing new circuitry through which muscarinic signalling may influence motivation, reward, and behavioural state. This research seeks to clarify the importance of receptor-specific cell populations and their connections to neural activity and disease-related behavioural traits.

Poster 16: Gabriela Gil (University of Strathclyde): Brain-wide, state-dependent GABAergic neural population dynamics in an Alzheimer’s disease mouse model

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, accounting for 60-70% of dementia cases. Amyloid beta accumulation is a pathological hallmark of AD, presumably arising from an imbalance between its production and clearance. The abnormal accumulation triggers synaptic and circuit impairments, leading to various cognitive deficits. While the development of novel immunotherapy is on the horizon, the efficacy remains suboptimal.

Sleep disruption has long been implicated as both an early indicator and an active contributor to the progression of AD. However, it remains unclear how amyloid pathology affects sleep-regulating circuits. Although GABAergic neurons are widely distributed and play a critical role in inhibiting wake-promoting circuits, we know little about how amyloid pathology disrupts GABAergic neural activity across the brain and sleep-wake cycles.

Here we address this issue in an AD mouse model. We express jGCaMP8s in GABAergic (GAD2+ or parvalbumin+) neurons across the brain of 5xFAD mice by creating triple transgenic mice. We use a novel multi-fiber photometry approach to monitor GABAergic neural signals across multiple regions. In conjunction with electrophysiology and pupillometry, we characterize the state-dependence of GABAergic neural population activity. In the session, we will also discuss how the disruption of brain-wide, state-dependent GABAergic neural activity impairs sleep-wake regulation in AD.

Poster 17: Isla Barnarard (University of Dundee): Effects of focused ultrasound thermal neuromodulation of the mediodorsal thalamus on value-based decision making

Background

Low-temperature sonications are routine within MRgFUS neurosurgery, depositing measurable acoustic and thermal energy without ablation. Previous work indicates modulation of the mediodorsal thalamic nucleus (MDn) alters choice stochasticity. In patients undergoing MRgFUS for essential tremor, we test whether low-temperature MD sonication measurably shifts exploration–exploitation behaviour.

Methods

A four-armed restless bandit task, adapted for periprocedural use, is delivered pre-operatively and repeated after brief non-ablative MDn thermal exposure. Real-time MR thermometry confirms thermal doses remain within subabaltive thresholds. Planar thermography maps extracted postoperatively validate subject-specific acoustic and thermal fields computed in-silico, giving volumetric estimates of low-dose energy deposition and spatial extent. Behavioural data are fitted with hierarchical Bayesian Kalman plus softmax-with-exploration-and-perseveration (SMEP) models. Patients sonicated at VIM provide an active control.

Results

Following MD sonication (n = 16), exploitative choices rose from 0.63 to 0.71, with reduced directed (0.13→0.09) and random (0.24→0.20) exploration; VIM controls (n = 15) showed no shift (0.68, 0.68). Group-level reward sensitivity (β) increased credibly after MD sonication (posterior mean 0.14→0.20, non-overlapping credible intervals); VIM posteriors were unchanged (0.14→0.15).

This links quantified acoustic–thermal dose to measurable change in decision making, integrating cognitive assessment within MRgFUS neurosurgery.

Poster 18: Monika Bielska (University of Glasgow): Evidence of distinct and overlapping pathways between parahippocampal formation and anterior thalamus

Spatial navigation arises from interactions between multiple neural circuits. Place cells, which represent animal’s location, were originally observed in the hippocampus but have recently been found in the anteromedial (AM) and anteroventral (AV) thalamic nuclei. However, since there is no direct projection from hippocampus proper to anterior thalamus, the source of thalamic place information remains unclear. Although segregation of AM and AV inputs has been reported in the subiculum, it is unknown whether there is any overlap in subicular neurons projecting to AM and AV. We performed pairwise injections of retrograde tracers CTb-488 and CTb-555 into the AM and AV, respectively, and examined the distribution of presynaptic partners. Dual-labelled cells were found across the brain but represented a small fraction of all projections. In dorsal subiculum, collateral projections were scarce, and populations were segregated: AM-projecting cells were found in the proximal, while AV afferents were located in distal subiculum. Such segregation was not observed in other regions, suggesting distinct, parallel information streams from the subiculum – a major hippocampal output – to anterior thalamus. This implies that spatial information in the AM and AV may come from distinct subicular subregions. Future experiments will investigate functional differences between these circuits in spatial navigation.