EPFL: An extended and improved CCFv3 annotation and Nissl atlas of the entire mouse brain

Glad to share Dr. Sebastien Piluso's work on the new atlas version paper, emerging from a long-standing research effort at the Blue Brain Project, is officially out in Imaging Neuroscience!

https://lnkd.in/dGdYhWyC

This work not only presents the first atlas covering the mouse central nervous system, but also provides anatomical reference data that unlock precise atlas segmentation of experimental brain images.

We even aim to shift the conceptualization of brain atlases from a single-volume reference model to a more versatile, next-generation framework.
This paves the way for large-scale brain image segmentation and the automated analysis of massive datasets using efficient, automated, and reproducible tools.

To showcase the capabilities of this dataset, we generated the first cellular atlas of the entire mouse brain, automatically identifying the coordinates, anatomical regions, and cell types of all its ~70 million constituent neurons. Additionally, we created an isotropic 10 μm-resolution average Nissl template from over 80,000 histological sections, revealing unprecedented anatomical contrasts without using interpolation.

Finally, these data serve as the foundational basis for constructing a precise and generic model of a digital mouse brain, now maintained by the Open Brain Institute. We have succeeded in bridging both ends by converting post-mortem anatomical images directly into realistic in silico data, which represents a significant step forward in the field of brain simulation.

Do not hesitate to explore, use, and share widely with colleagues!

I would like to thank all those who contributed to this work, and give a special thank you to Cyrille Favreau for the wonderful image visualization and Karin Holm for invaluable editorial support!

EPFL: A multiscale electro-metabolic model of a rat neocortical circuit reveals the impact of ageing on central cortical layers

🧠 Why does the brain demand so much energy? What happens when that supply falters with age?

In this study, we present a multiscale model of electro-metabolic coupling in a digitally reconstructed rat neocortex. By combining detailed electrophysiological modeling with neuro-glial-vascular (NGV) metabolic dynamics, we explore how energy demand varies across neurons and circuits, and how ageing disrupts this balance.

Key insights: 

🔹 Energy use varies by neuron type and circuit location

 🔹 Middle cortical layers are especially vulnerable to age-related metabolic decline

 🔹 Our model bridges single-cell metabolism and whole-circuit function 

We’re excited that this work brings us closer to understanding how energy dynamics influence brain ageing. 🙏

A big thank you to everyone in the EPFL Blue Brain Project - A Swiss Brain Initiative who contributed over the years to advancing neuroscience. In particular, I’d like to recognize the amazing contributors to this article: Alessandro Cattabiani, Darshan Mandge, Polina Shichkova, James Isbister, Jean Jacquemier, James Gonzalo King, Henry Markram, and Daniel Keller.

💫 Special thanks to Cyrille Favreau and Elvis Boci for their beautiful work on Figure 1 (below👇), Karin Holm for editorial support, and everyone else who helped shape this research.

📖 Read more: https://lnkd.in/dg-A-rVQ

EPFL: Discover the Beauty of the Brain

I'm beyond excited to share something truly special from my work with the Blue Brain Project!

Over the past decade (2014–2024), I’ve crafted a breathtaking collection of computational neuroscience visuals using Blue Brain Brayns 1.1.0 (up to 2019) and Blue Brain BioExplorer (from 2020 onward). 

All these mesmerizing images and videos are now publicly available under the EPFL/Blue Brain Project CC BY 4.0 License.

You can download the entire collection from my online gallery.

Let’s make the wonders of computational neuroscience accessible to everyone, one incredible visual at a time.

 Dive in and explore!

EPFL: Modeling of Blood Flow Dynamics in Rat Somatosensory Cortex

Background: 

The cerebral microvasculature forms a dense network of interconnected blood vessels where flow is modulated partly by astrocytes. Increased neuronal activity stimulates astrocytes to release vasoactive substances at the endfeet, altering the diameters of connected vessels.

Methods:

 Our study simulated the coupling between blood flow variations and vessel diameter changes driven by astrocytic activity in the rat somatosensory cortex. We developed a framework with three key components: coupling between the vasculature and synthesized astrocytic morphologies, a fluid dynamics model to compute flow in each vascular segment, and a stochastic process replicating the effect of astrocytic endfeet on vessel radii.

Visualization with NVIDIA Omniverse

Results: 

The model was validated against experimental flow values from the literature across cortical depths. We found that local vasodilation from astrocyte activity increased blood flow, especially in capillaries, exhibiting a layer-specific response in deeper cortical layers. Additionally, the highest blood flow variability occurred in capillaries, emphasizing their role in cerebral perfusion regulation. We discovered that astrocytic activity impacted blood flow dynamics in a localized, clustered manner, with most vascular segments influenced by two to three neighboring endfeet.

Conclusions: 

These insights enhance our understanding of neurovascular coupling and guide future research on blood flow-related diseases.

Link to the publication: https://www.mdpi.com/2227-9059/13/1/72

Activation of the Speculative Santhalamus Claustex by Festive Auditory and Olfactory Stimuli 😂

The theoretical construct of the Santhalamus Claustex postulates its role as a speculative brain region crucial in the synthesis of emotions and the consolidation of memories. Envisioned as an intricate network of neural clusters, this hypothetical region purportedly orchestrates an interplay between emotional processing and memory formation within the human brain.

Recent suppositions suggest a potential link between the activation of the Santhalamus Claustex and exposure to specific sensory stimuli during festive occasions. It is hypothesized that the repetitive exposure to traditional auditory cues, such as festive carols, and the olfactory experience induced by the inhalation of mulled wine’s aromatic compounds, may elicit activity within this speculative neural territory.

 Brain simulation refers to the process of creating a computer-based model or simulation that mimics the functions and behaviors of the brain. This ambitious field of research aims to understand, replicate, and potentially emulate the complex workings of the brain in a digital environment. 

Simulating the brain requires understanding and replicating the intricate connections between neurons, known as synapses. Modeling how information is transmitted and processed through these connections is a crucial aspect of brain simulation.

Merry XMas!

Data sources:

- Simulation: BluePyOpt (https://github.com/BlueBrain/BluePyOpt)
- Morphologies: Neuromorpho.org (https://neuromorpho.org/)

EPFL: Breakdown and repair of the aging brain metabolic system

The study presented explores the complex relationship between the aging brain, energy metabolism, blood flow and neuronal activity by introducing a comprehensive, data-driven molecular model of the neuro-glial vascular system, including all key enzymes, transporters, metabolites, and blood flow vital for neuronal electrical activity with 16’800 interaction pathways. We find significant alterations in metabolite concentrations and differential effects on ATP supply in neurons and astrocytes and within subcellular compartments within aged brains, and identify reduced Na⁺/K⁺-ATPase as the leading cause of impaired neuronal action potentials. The model predicts that the metabolic pathways cluster more closely in the aged brain, suggesting a loss of robustness and adaptability. Additionally, the aged metabolic system displays reduced flexibility, undermining its capacity to efficiently respond to stimuli and recover from damage. Through transcription factor analysis, the estrogen-related receptor alpha (ESRRA) emerged as a central target connected to these aging-related changes. An unguided optimization search pinpointed potential interventions capable of restoring the brain’s metabolic flexibility and restoring action potential generation. These strategies include increasing the NADH cytosol-mitochondria shuttle, NAD+ pool, ketone β-hydroxybutyrate, lactate and Na⁺/K⁺-ATPase and reducing blood glucose levels. The model is open-sourced to help guide further research in brain metabolism.

Publication: https://www.biorxiv.org/content/10.1101/2023.08.30.555341v2 

Scientific Collaborator: Polina Shichkova, Ph. D

Data visualization tool: Blue Brain BioExplorer

EPFL: Neuromodulation of neocortical microcircuitry: a multi-scale framework to model the effects of cholinergic release

Neuromodulation of neocortical microcircuits is one of the most fascinating
and mysterious aspects of brain physiology. Despite over a century of research,
the neuroscientific community has yet to uncover the fundamental biological organizing principles underlying neuromodulatory release.

Phylogenetically, Acetylcholine (ACh) is perhaps the oldest neuromodulator, and one of the most well-studied. ACh regulates the physiology of neurons and synapses, and modulates neural microcircuits to bring about a reconfiguration of global network states. ACh is known to support cognitive processes such as learning and memory, and is involved in the regulation of arousal, attention and sensory processing. While the effects of ACh in the neocortex have been characterized extensively, integrated knowledge of its mechanisms of action is lacking.

Furthermore, the ways in which ACh is released from en-passant axons originating in subcortical nuclei are still debatable. Simulation-based paradigms play an important role in testing scientific hypotheses, and provide a useful framework to integrate what is already known and systematically explore previously uncharted territory.

Importantly, data-driven computational approaches highlight gaps in current knowledge and guide experimental research. To this end, I developed a multi-scale model of cholinergic innervation of rodent somatosensory cortex comprising two distinct sets of ascending projections implementing either synaptic (ST) or volumetric transmission (VT). The model enables the projection types to be combined in arbitrary proportions, thus permitting investigations of the relative contributions of these two transmission modalities.

Using our ACh model, we find that the two modes of cholinergic release act in concert and have powerful desynchronizing effects on microcircuit activity. Furthermore we show that this modeling framework can be extended to other neuromodulators, such as dopamine and serotonin, with minimal constraining data. In summary, our results suggest a more nuanced view of neuromodulation in which multiple modes of transmitter release - ST vs VT - are required to produce synergistic functional effects.

Publication: https://infoscience.epfl.ch/entities/publication/0a69c342-ac83-4fa3-bc08-44b886969d60

Scientific Collaborator: Cristina Colangelo, Ph.D

Data visualization tool: Blue Brain BioExplorer 

NVIDIA: Wanted! Business Card on a Mission

Wanted: one ambitious business card, last seen in 2012, lounging on a bench in front of NVIDIA’s former US offices.

Picture it: 2012, bright-eyed me, full of dreams, standing at the gates of NVIDIA, the tech giant of my fantasies. Armed with nothing but a neatly printed business card and an overabundance of optimism, I did what any sensible person would do: I left my card on a bench. The strategy? Genius. The logic? Questionable. But hey, in my head, it was the ultimate mic drop. Someone would find it? get intrigued?

Instead, life had other plans, steering me toward EPFL's Blue Brain Project, where I spent a decade on the wildest, most rewarding ride of my career. From unraveling neural mysteries to building tools that merged science and creativity.

Still, every now and then, I wonder—what happened to that card? Is it still there, weathered and waiting? If you find it, congratulations! And guess what? It’s still valid, and I’d love to hear from you.

NVIDIA: Bringing Brain Simulations to Life with NVIDIA Omniverse

In computational neuroscience, visualizing the brain is crucial to understanding its complex behavior. NVIDIA Omniverse is revolutionizing this process by turning neuron simulations into vibrant, dynamic visualizations—bridging the gap between data and discovery.

 

Using Omniverse, we can map electrical currents in neurons to vivid colors, creating real-time, interactive displays of brain activity. Researchers can zoom into individual neurons, explore neural networks, and observe dynamic changes in activity—all in stunning 3D.

Omniverse empowers researchers to build digital twins of brain regions. These twins enable the simulation of diseases, testing of interventions, and real-time collaboration. Its USD-based scalability and Python integration make it an unparalleled tool for neuroscience visualization.

From advancing research on neurological disorders to immersive education tools, Omniverse empowers neuroscientists to transform raw data into actionable insights. 

Data sources:

- BluePyOpt: https://github.com/BlueBrain/BluePyOpt

- Neuromorpho.org: https://neuromorpho.org/

NVIDIA: Blood flow visualization with Omniverse

Today, I explored the incredible flexibility of NVIDIA's fully scriptable Omniverse platform by developing an interactive blood flow visualization. The dataset, originally generated using AstroVascPy (https://lnkd.in/d3dxN6yJ), was initially in SONATA format and later converted into OpenUSD for compatibility. The simulation data was integrated as custom attributes directly tied to the streamline geometry, allowing for a dynamic, frame-based rendering.

With each simulation frame, the radius and color of the streamlines update automatically, reflecting changes in the dataset in real time. This approach combines the power of Python scripting with the robust visualization capabilities of Omniverse, making it effortless to bring complex, multi-dimensional simulation data to life.

Omniverse's fully scriptable architecture played a critical role in streamlining this process, enabling custom workflows tailored to specific datasets and visualization requirements. This project highlights how the platform can bridge scientific simulation and interactive visualization, offering researchers powerful tools to analyze and present intricate biological processes with unprecedented clarity.

- AstroVascPy: https://github.com/BlueBrain/AstroVascPy

NVIDIA: Playing with Omniverse and Exploring Brain Digital Twins in High-Quality 3D

I’ve been having a blast experimenting with NVIDIA Omniverse, using neuroscience data to delve into the concept of brain digital twins. While it’s not a finished solution (yet), it’s an incredible sandbox for interactive visualization and testing the limits of what’s possible in rendering complex neural structures.

Bringing brain models to life in immersive, high-quality 3D is both captivating and full of promise. Omniverse provides a glimpse into a future where neuroscience can be explored in entirely new ways, making it an exciting platform to experiment with.

This is just the beginning, but the potential is huge.

Data sources:
- EPFL Blue Brain Project: https://lnkd.in/gH3cgPAs
- Tractome Dataset: https://lnkd.in/dGwgsv5z
- Flywire: https://flywire.ai

EPFL: Modeling of blood flow dynamics in the rat somatosensory cortex

I'm very proud of this publication, where I contributed to the visualization of a comprehensive simulation framework to study neurovascular coupling in the rat somatosensory cortex. This study sheds light on the fascinating interplay between astrocytic activity and cerebral microvasculature, revealing how astrocytic endfeet drive localized vessel diameter changes, particularly in capillaries, to regulate blood flow. A huge congratulations to Stéphanie Battini for her outstanding work and for being such a fantastic collaborator—it’s been an absolute pleasure to work alongside you!

Publication: https://www.biorxiv.org/content/10.1101/2024.11.14.623572v1

Model: https://github.com/BlueBrain/AstroVascPy

Gource: A Tool for Validating Project Quality

Gource is an open-source visualization tool that animates your project's history, making it invaluable for assessing development quality, refactoring efforts, and overall contributions.

Validating Code Quality Through Visualizations

Gource visualizes refactoring by animating file changes, showing how files move, split, or consolidate over time. This helps developers and stakeholders quickly understand improvements in code quality, reduction of technical debt, and the effectiveness of refactoring efforts.

Assessing Project Structure and Stability

Gource illustrates the evolution of project structure as a dynamic tree, with commits visually highlighted. This allows teams to track development focus, identify potential problem areas, and validate the stability of critical components, ensuring the quality of the evolving codebase.

Recognizing Contributor Impact

Gource highlights individual contributions, bringing visibility to crucial but often-overlooked work like testing, infrastructure, and maintenance. By summarizing contributions, Gource helps validate each team member’s impact on the project's quality.

Demonstrating Project Health and Progress

Gource’s animations transform complex commit histories into clear, engaging visuals, allowing stakeholders to easily understand project health, growth, and quality improvements over time.

Conclusion

Gource is a powerful tool for validating and communicating project quality. It provides an engaging way to understand development progress, refactoring outcomes, and individual contributions, turning commit history into a meaningful story of continuous improvement.

Links

Gource: https://github.com/acaudwell/Gource

Demo Project: https://github.com/BlueBrain/BioExplorer/