The hippocampus is one of the most fascinating regions of the brain. Associated with the formation of memories, it also helps us navigate the world without getting lost. On the other hand, sensory cortices play an important role in how we perceive our environment and make appropriate movements, and in how our brain determines what to focus on and what to ignore. While both regions have been extensively studied and many of their secrets have been revealed, there is still much we do not understand about them due to the high complexity of the interacting parts, from the individual synapses and the zoo of different types of neurons, to the detailed connectivity rules. between them. To improve our understanding, EPFL researchers have built detailed computational models of these regions. By bringing together the neurons that make up these regions and describing the rules of their interactions through computer code, they can simulate brain activity in these regions and study the role of each part in the concert of brain activity.
Unlike previous models, these models were built with the exact three-dimensional geometry of their corresponding brain region. This opens the door to future refinements and testing of the models with new experimental data. By focusing on building general three-dimensional models, the models can also be used to explore a wide range of phenomena.
This is not an easy process. Describing the rules that govern the regions and turning them into computer simulations required the participation of many experts who have encountered and know these rules. Therefore, the researchers have collaborated with more than 80 colleagues around the world to develop the largest and most detailed models of these brain regions. “The integration of data from multiple sources and collaboration between scientists are the strengths of these models, although they also presented challenges,” says Dr. Armando Romani, leader of Blue Brain’s Circuits group. “By addressing these obstacles, the models have become more robust, adaptable and accessible to the broader scientific community.” They have now openly released the models to the scientific community along with the tools to study and use them. The models are described in four extensive articles, each focusing on different aspects.
In Modeling and simulation of neocortical micro- and meso-circuits. Part I, published in the magazine eLifeThe focus is on the anatomy of the somatosensory regions and their connectivity. Its main idea is that the shape of brain regions affects the structure of the brain networks that form within them and a description of how connectivity at different scales comes together to form highly complex patterns. “Sometimes we are used to thinking about local and long-range connectivity as separate systems,” says Dr. Michael Reimann, leader of the Connectomics group at Blue Brain. “We were really surprised to see how the systems interact to form these types of very structured networks.”
Part II, published in eLife Along with the first article, it describes the physiology of the brain region and how it was modeled and validated at the synaptic, neuronal and network levels. “This allowed us to make predictions about how particular components of the brain, such as specific connectivity patterns, contribute to observations about cortical processing made by our experimental colleagues,” explains lead researcher Dr. James Isbister. “The 3D geometry of the model allows us to study the communication between areas of the brain and, what is more interesting, recreate experiments that combine complex laboratory methods, such as optogenetics, with approaches only possible in simulations, such as lesions between very specific populations” .
A third article in eLife explains how the model was further improved to include the process of synaptic plasticity, the fundamental mechanism that allows us to learn new information. Their knowledge concerns the complex rules that govern the processes that arise when millions of synapses undergo plasticity under live conditions, as in the living brain. “For a long time, simulations have focused on plasticity rules based on laboratory experiments, under artificial conditions,” says lead researcher Dr. Andras Ecker. “We wanted to explore plasticity in detailed networks and live“.
Finally, a fourth article in More biology presents a complete in silicone model of the rat CA1 region, which integrates diverse experimental data from synapse to network levels, including Schaffer collaterals (key conduits for information transfer and synaptic plasticity in the hippocampal circuit) as well as effects of the neurotransmitter acetylcholine. “Each component was rigorously tested and validated, and we made all input data, assumptions and methodologies completely transparent,” adds Dr. Romani. “Now accessible in hippocampushub.eu“This model serves as a flexible tool for scientists, providing extensive analyzes and an interface to support future research on the hippocampus.”
Three additional journal articles and three preprint manuscripts demonstrate the value of the models to the scientific community. In them, the models have been used to study inter-area processing, the neuronal code and the relationship between connectivity and neuronal activity. The results of plasticity simulations were compared with electron microscopy data and the effect of the predicted motif on synapse strength was confirmed. “We have known for a long time that brain networks are complex and follow specific rules,” explains lead researcher Dr. Egas Santander. “The model allows us to begin to explore the reasons for those rules.”