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Bugeon, S.

Publications and source records attributed to Bugeon, S..

7 recordsLinked to original sources

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↗

The SAFE Labs Handbook: community-driven commitments for group leaders to improve lab culture

Creating positive and equitable lab environments has become a growing priority for the scientific community and funders of scientific research. Research institutions typically respond to this need by providing mandatory or optional training opportunities for their staff. However, there is no established resource for group leaders to improve their lab culture with concrete action points for implementation. Here, we introduce the SAFE Labs Handbook: a collection of thirty "commitments" which can be verifiably actioned without requiring institutional support. These commitments were collaboratively developed by thirteen group leaders in life sciences, from institutions across eight countries, instigated through the 2024 SAFE Labs workshop. The importance of each commitment has been scored by more than 200 researchers, at various career stages, from more than twenty countries. Even though all commitments were rated as significantly important by scientists from all career stages, implementation rates were notably low (< 25%). Lab members reported higher importance scores than group leaders, with large divergences indicating where group leaders may underestimate the potential impact on lab culture. Indeed, the overall implementation rate was correlated with importance score for group leaders, but not lab members. Strikingly, more than 95% of group leaders said they would consider implementing the handbook commitments. Given the high importance-scores and low-implementation rates, the SAFE Labs Handbook represents a unique, community-driven tool with significant potential to improve lab culture on a global scale.

scientific communication and education↗

Longitudinal tracking of neuronal activity from the same cells in the developing brain using Track2p

Understanding cortical circuit development requires tracking neuronal activity across days in the growing brain. While in vivo calcium imaging now enables such longitudinal studies, automated tools for reliably tracking large populations of neurons across sessions remain limited. Here, we present a novel cell-tracking method based on sequential image registration, validated on calcium imaging data from the barrel cortex of mouse pups over one postnatal week. Our approach enables robust long-term analysis of several hundreds of individual neurons, allowing quantification of neuronal dynamics and representational stability over time. Using this method, we identified a key developmental transition in neuronal activity statistics, marking the emergence of arousal state modulation. Beyond this key finding, our method provides an essential tool for tracking developmental trajectories of individual neurons, which could help identify potential deviations associated with neurodevelopmental disorders.

neuroscience↗

Adaptation shapes the representational geometry in mouse V1 to efficiently encode the environment

Sensory adaptation dynamically changes neural responses as a function of previous stimuli, profoundly impacting perception. The response changes induced by adaptation have been characterized in detail in individual neurons and at the population level after averaging across trials. However, it is not clear how adaptation modifies the aspects of the representations that relate more directly to the ability to perceive stimuli, such as their geometry and the noise structure in individual trials. To address this question, we recorded from a population of neurons in the mouse visual cortex and presented one stimulus (an oriented grating) more frequently than the others. We then analyzed these data in terms of representational geometry and studied the ability of a linear decoder to discriminate between similar visual stimuli based on the single-trial population responses. Surprisingly, the discriminability of stimuli near the adaptor increased, even though the responses of individual neurons to these stimuli decreased. This improvement arose mainly from how adaptation reshaped the geometry of the mean population responses, with changes in the noise structure playing a minor role. Locomotion modulated the population responses along a direction largely independent of adaptation, allowing the adaptation-induced increase in discriminability to persist during locomotion. Finally, artificial neural networks trained to reconstruct the visual stimulus under metabolic constraints reproduced the increase in discriminability and the decrease in responses. The paradoxical effects of adaptation are thus consistent with the efficient coding framework, allowing the brain to improve the representation of frequent stimuli while limiting the associated metabolic cost.

neuroscience↗

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↗

Morphofunctional deficits in the cerebral cortex of NeuroD2 mutant mice are associated with autism/schizophrenia-like behaviors

We identified seven families associating NEUROD2 pathogenic mutations with ASD and intellectual disability. To get insight into the pathophysiological mechanisms, we analyzed cortical development in Neurod2 KO mice. Cortical projection neurons (CPNs) over-migrated during embryogenesis, inducing abnormal thickness and laminar positioning of cortical layers. At juvenile ages, dendritic spine turnover and intrinsic excitability were increased in L5 CPNs. Differentially expressed genes in Neurod2 KO mice were enriched for voltage-gated ion channels, and the human orthologs of these genes were strongly associated with ASD. Furthermore, adult Neurod2 KO mice exhibited core ASD-like behavioral abnormalities. Finally, by generating Neurod2 conditional mutant mice we demonstrate that forebrain excitatory neuron-specific Neurod2 deletion recapitulates cellular and behavioral ASD phenotypes found in full KO mice. Our findings demonstrate crucial roles for Neurod2 in cortical development and function, whose alterations likely account for ASD and related symptoms in the newly defined NEUROD2 mutation syndrome.

neuroscience↗

Neuronal integration in the adult olfactory bulb is a non-selective addition process

Adult neurogenesis is considered a competition in which neurons scramble during a critical period for integration and survival. Moreover, newborn neurons are thought to replace preexisting ones that die. Despite a wealth of evidence supporting this model, systematic in vivo observations of the process are still scarce. We used 2-photon imaging to study neuronal integration and survival directly in the olfactory bulb (OB) of living mice. Long-term tracking of over 1400 neurons demonstrated that cell-loss in the OB is virtually absent. Neuronal death resembling a critical period was induced by standard doses of BrdU or EdU, but disappeared when low doses of EdU were used, demonstrating toxicity. Finally, we demonstrate that the OB grows throughout life. This shows that neuronal selection during OB-neurogenesis does not occur during integration and argues against the existence of a critical period. Moreover, the OB is not a \"turnover\" system but shows lifelong neuronal addition.

neuroscience↗