Università degli studi di Modena e Reggio Emilia

The first 3D model of the human hippocampus neural network has been created

The first 3D model of the human hippocampus has been developed thanks to the collaboration between researchers from the Department of Biomedical, Metabolic and Neural Science of Unimore, the Institute of Biophysics of the National Research Council (CNR-Ibf), the Institut de Neurosciences des systèmes of Marseille and the Universities of Sassari and Pavia: a revolutionary study for predictive medicine and the creation of virtual patients and digital twins

Researchers from the Department of Biomedical, Metabolic and Neural Science at Unimore, in collaboration with the Institute of Biophysics of the National Research Council (CNR-Ibf), the Institut de Neurosciences des systèmes in Marseille and the Universities of Sassari and Pavia, have created the first in silico 3D model of the CA1 region of the human hippocampus.

The study, published in the journal Nature Computational Science , describes the methodology that was developed to create the structure and connectivity of this brain area. The authors emphasise how this methodology will enable the production of large-scale circuit models of other human brain regions, opening up important perspectives for predictive medicine and the creation of virtual patients and digital twins.

From very high-resolution images of a human brain, the researchers were able to reconstruct the positioning in the hippocampal volume of approximately 5.3 million neurons. A specially developed connectivity algorithm based on the generation of synthetic neuronal morphologies made it possible to probabilistically map the connections between neurons in order to reconstruct the entire neuronal network consisting of approximately 40 billion synapses.

The work completed by the researchers in Modena focuses on the hippocampus, a brain structure involved in various cognitive functions such as learning, memory and spatial processing, as well as being strongly implicated in the pathogenesis of various neurological diseases such as epilepsy and neurodegenerative diseases such as Alzheimer's. This study represents a first result of the work of the groups belonging to the 'Ebrains-Italy' research infrastructure funded by Mur, through the European Commission (Next-Generation EU), within the framework of the National Recovery and Resilience Plan (NRRP) coordinated by the CNR, which helped fund this research.

'Our approach,' comments Dr Daniela Gandolfi, first author of the article, 'is based on the analysis of high-resolution images of the human brain and simplified modelling of the morphological properties of individual neurons. From the intersection probability of synthetic morphologies we are able to derive the connectivity between neurons and thus simulate the functional activity of the network. In particular, we verified that the spatial distribution of the density of neurons in the 3D model thus obtained was congruent with literature data on the human hippocampus’.

'At NILab (Neuromorphic Intelligence Laboratory),' Gandolfi concludes, 'we develop models of brain circuits to expand knowledge in neuroscience. Thanks to the work of young researchers, PhD students and undergraduates, we are developing models of other regions of the human hippocampus, e.g. the CA3 region, and through collaboration with the University of Marseille we are working to integrate such models into a digital twin of the human brain (The Virtual Brain)’.

Researchers are sharing both the dataset and the extraction methodology on the EBRAINS platform, making the data readily available to the neuroscientific community.

'Generating models of human brain circuits with cellular resolution is a particularly complex task for several reasons,' explains Prof. Jonathan Mapelli. Not only are data on the functionality of individual human neurons almost absent, but also the amount of images on cell morphologies available to the scientific community is limited. Reproducing the activity of an entire brain reason means having to simultaneously solve billions of equations concerning the activation of neurons and synapses. The challenge was to develop a strategy that could overcome the scarcity of data and the high computational demands. Analysing brain functions through mathematical models capable of describing their cellular and synaptic mechanisms makes it possible to analyse conditions that cannot be explored experimentally and offers the possibility of developing and then testing new therapeutic and pharmacological approaches’.

'The research just published in a top-ranking journal by Dr. Gandolfi, Prof. Mapelli and their Italian and foreign collaborators,' adds Prof. Michele Zoli, Director of the Department of Biomedical, Metabolic and Neural Sciences, 'is of great relevance as it answers one of the most topical questions in neuroscience, namely identifying, or at least hypothesising, the global activity of a complex brain structure from the myriad of specific information gathered from neurobiological research. The creation of morpho-functional models consistent with the actual number of neurons, their spatial relationships and cytological heterogeneity, and their connectivity in a specific brain region is a fundamental step in understanding their physiological functioning as well as their possible pathological alterations’.

Categorie: International - english