Biology subjects

Orme, D.

Publications and source records attributed to Orme, D..

5 recordsLinked to original sources

bioRxiv2026

Spatially resolved transcriptomic identification of thousands of neurons recorded in vivo.

Transcriptomics has transformed our understanding of the brain, but assigning transcriptomic identities to neurons recorded in vivo remains challenging at scale. Existing platforms can pair transcriptomic identity with two-photon calcium imaging in small populations of approximately 100 neurons, but they require recorded cells to be sparse and therefore cannot be applied to large population recordings. Here, we present coppaFISH 3D, a spatially resolved transcriptomics method, and CASTalign, an in silico alignment framework, which together enable transcriptomic identification of thousands of simultaneously recorded cells. coppaFISH 3D detects hundreds of genes in thick 50m fixed sections while preserving tissue integrity, enabling both 3D registration to in vivo imaging and integration with immunofluorescence labelling. The platform is fully powered by open chemistry and open source software, runs on commodity hardware, and can be performed at very low cost per section. It therefore enables transcriptomic identification of recorded neurons at scale, making it possible to study how transcriptomic identity shapes activity in neural populations.

neuroscience↗

bioRxiv2026

Learning temporal structure engages hippocampus and guides value-based behaviour

The ability to learn and exploit structured relationships between events is fundamental to adaptive behaviour and episodic-like memory, yet the neural mechanisms that support such learning remain poorly understood. Progress has been limited by the difficulty of dissociating relational structure from sensory cues, value, and motor output in experimentally tractable tasks. Here we introduce a temporally structured olfactory task for mice that isolates relational structure from cue identity and reward statistics. Mice rapidly learned to use the ordered relationship between two sequentially presented odours to predict outcome. Because individual odours were equally associated with reward across contexts, their predictive value depended entirely on their relationship to preceding cues. Behavioural analyses and reinforcement learning models revealed a gradual shift to the use of structured representations as learning progressed. Dopamine activity in the nucleus accumbens reflected this transition. Over learning, identical sensory inputs became associated with opposite predicted outcomes depending only on their temporal position, consistent with dopamine prediction errors reflecting latent task structure rather than cue identity. Trial-by-trial variability in dopamine dynamics was quantitatively captured by the same models that described behavioural strategy, linking dopamine prediction errors directly to these learned structural representations. Finally, using a matched control task that preserved sensory input and reward statistics while eliminating structure, we found that learning and using temporal structure selectively increased ventral hippocampal activity. Together, these results establish a minimal, non-spatial paradigm for studying structural learning in mice, link behavioural representations to dopamine signalling, and show that isolating relational structure from sensory and reward confounds selectively recruits hippocampal circuitry long theorised to support it.

neuroscience↗

bioRxiv2023

Surveillance of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential

There has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses in 48 faecal samples from 16 of the 17 bat species breeding in the UK, collected through a bat rehabilitation and conservationist network. We recovered nine (two novel) complete genomes across six bat species: four alphacoronaviruses, a MERS-related betacoronavirus, and four closely related sarbecoviruses. We demonstrate that at least one of these sarbecoviruses can bind and use the human ACE2 receptor for infecting human cells, albeit suboptimally. Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. However, mutating this motif to an FCS does not enable spike cleavage. Overall, while UK sarbecoviruses would require further molecular adaptations to infect humans, their zoonotic risk is unknown and warrants closer surveillance.

genomics↗

bioRxiv2021

A transcriptomic axis predicts state modulation of cortical interneurons

Transcriptomics has revealed the exquisite diversity of cortical inhibitory neurons1-7, but it is not known whether these fine molecular subtypes have correspondingly diverse activity patterns in the living brain. Here, we show that inhibitory subtypes in primary visual cortex (V1) have diverse correlates with brain state, but that this diversity is organized by a single factor: position along their main axis of transcriptomic variation. We combined in vivo 2-photon calcium imaging of mouse V1 with a novel transcriptomic method to identify mRNAs for 72 selected genes in ex vivo slices. We used transcriptomic clusters (t-types)4 to classify inhibitory neurons imaged in layers 1-3 using a three-level hierarchy of 5 Families, 11 Classes, and 35 t-types. Visual responses differed significantly only across Families, but modulation by brain state differed at all three hierarchical levels. Nevertheless, this diversity could be predicted from the first transcriptomic principal component, which predicted a cell types brain state modulation and correlations with simultaneously recorded cells. Inhibitory t-types with narrower spikes, lower input resistance, weaker adaptation, and less axon in layer 1 as determined in vitro8 fired more in resting, oscillatory brain states. Transcriptomic types with the opposite properties fired more during arousal. The former cells had more inhibitory cholinergic receptors, and the latter more excitatory receptors. Thus, despite the diversity of V1 inhibitory neurons, a simple principle determines how their joint activity shapes state-dependent cortical processing.

neuroscience↗

bioRxiv2017

Robust, real-time and autonomous monitoring of ecosystems with an open, low-cost, networked device

O_LIAutomated methods of monitoring ecosystems provide a cost-effective way to track changes in natural systems dynamics across temporal and spatial scales. However, methods of recording and storing data captured from the field still require significant manual effort.\nC_LIO_LIHere we introduce an open source, inexpensive, fully autonomous ecosystem monitoring unit for capturing and remotely transmitting continuous data streams from field sites over long time-periods. We provide a modular software framework for deploying various sensors, together with implementations to demonstrate proof of concept for continuous audio monitoring and time-lapse photography.\nC_LIO_LIWe show how our system can outperform comparable technologies for fractions of the cost, provided a local mobile network link is available. The system is robust to unreliable network signals and has been shown to function in extreme environmental conditions, such as in the tropical rainforests of Sabah, Borneo.\nC_LIO_LIWe provide full details on how to assemble the hardware, and the open-source software. Paired with appropriate automated analysis techniques, this system could provide spatially dense, near real-time, continuous insights into ecosystem and biodiversity dynamics at a low cost.\nC_LI

ecology↗