Periodic Reporting for period 1 - HESSP (Hippocampus Extracellular Space Simulator Project (HESSP))
Reporting period: 2020-09-01 to 2022-08-31
Understanding the human brain is one of the biggest scientific challenges of the 21st century, and this endeavour has led the European Union to launch the Human Brain Project (HBP) as a FET flagship project. However, even a flagship project such as the HBP cannot study all aspects of the human brain. One aspect that is not covered by the HBP is the extracellular space (ES). The ES of the brain is important in the field of neuropharmacology because it is key to the successful delivery of drugs to the neurons. Also, the importance of the metabolite clearance activity of the ES has led to proposing that a dysfunction of this process plays a role in neurodegenerative diseases. However, no initiative exists to create an ES simulation software that improves the research.
To address this lack of simulation software, the Hippocampus Extracellular Space Simulator Project (HESSP) is going to be executed. The HESSP’s goal is to develop a simulation software for how substances released by neurons and chemical substances that pass the blood-brain barrier diffuse through the ES. Specifically, the HESSP will create a software that simulates the diffusion process in the ES of the mouse’s hippocampus. The HESSP is an interdisciplinary project that involves computer science, neuroscience and pharmacology, and it addresses the challenge of developing a software architecture to simulate a diffusion process highly complex due to its number of elements formed. The hippocampus was chosen because it is a well-known structure, the results can be tested, and it is the earliest brain structure affected in Alzheimer’s disease (AD). The principal researcher, Dr Sergio Miguel Tomé, will carry out a fellowship to develop a simulation software of the extracellular space (ES) of the hippocampus. This fellowship will be completed at SUNY Downstate Medical Center in Brooklyn, New York, under the supervision of Dr. Herman Moreno, for 24 months. The principal researcher will have an advisory committee that includes Dr. Herman Moreno, Dr. Sabina Hrabetova and Dr. William Lytton. The principal researcher will then return to the University of Salamanca for 12 months and work under the supervision of Dr. Juan M. Corchado and with the support Dr. Corchado’s research group BISITE. Also, Dr. Ángel F. Porteros from INCYL (Institute of Neuroscience of Castilla y Leon, USAL University Center) will help in the creation of a line of research to address projects in computational neuroscience.
This project focuses on three main objectives:
• O1. Create a model of the ES of the mouse hippocampus.
• O2. Create simulation software for substances in the mouse hippocampus.
• O3. Make predictions using the simulation software.
The HESSP will open a frontier line of research at the University of Salamanca in collaboration with leading scientists in ES and neurodegenerative diseases. Additionally, the principal researcher will acquire frontier knowledge in the simulation of complex biophysical processes and in neuroscience.
To address this lack of simulation software, the Hippocampus Extracellular Space Simulator Project (HESSP) is going to be executed. The HESSP’s goal is to develop a simulation software for how substances released by neurons and chemical substances that pass the blood-brain barrier diffuse through the ES. Specifically, the HESSP will create a software that simulates the diffusion process in the ES of the mouse’s hippocampus. The HESSP is an interdisciplinary project that involves computer science, neuroscience and pharmacology, and it addresses the challenge of developing a software architecture to simulate a diffusion process highly complex due to its number of elements formed. The hippocampus was chosen because it is a well-known structure, the results can be tested, and it is the earliest brain structure affected in Alzheimer’s disease (AD). The principal researcher, Dr Sergio Miguel Tomé, will carry out a fellowship to develop a simulation software of the extracellular space (ES) of the hippocampus. This fellowship will be completed at SUNY Downstate Medical Center in Brooklyn, New York, under the supervision of Dr. Herman Moreno, for 24 months. The principal researcher will have an advisory committee that includes Dr. Herman Moreno, Dr. Sabina Hrabetova and Dr. William Lytton. The principal researcher will then return to the University of Salamanca for 12 months and work under the supervision of Dr. Juan M. Corchado and with the support Dr. Corchado’s research group BISITE. Also, Dr. Ángel F. Porteros from INCYL (Institute of Neuroscience of Castilla y Leon, USAL University Center) will help in the creation of a line of research to address projects in computational neuroscience.
This project focuses on three main objectives:
• O1. Create a model of the ES of the mouse hippocampus.
• O2. Create simulation software for substances in the mouse hippocampus.
• O3. Make predictions using the simulation software.
The HESSP will open a frontier line of research at the University of Salamanca in collaboration with leading scientists in ES and neurodegenerative diseases. Additionally, the principal researcher will acquire frontier knowledge in the simulation of complex biophysical processes and in neuroscience.
The main goal of the HESSP is developing a software to simulate the diffusion of substance through nervous tissue, the Hybrid Advanced Particles Simulator (HAPS). The HESSP project started in September 2020. During the first year of the project, Dr Miguel Tomé worked on creating a model of the ES of the mouse hippocampus by designing data structures so that the simulator can cover different morphological models of nervous tissue and programming algorithms to generate the geometry of it. In addition, a graphical interface to show the geometry of the environment was implemented. Figure 1 shows the graphical interface created to allow the user visualising a geometrical environment where to simulate a diffusion process. Every fifteen days, Dr Miguel Tomé attended a videoconference with Dr Herman Moreno and Dr Sabina Hrabetova to discuss the evolution of the project and anatomical data about brain tissues
During the second year of the project, Dr Miguel-Tomé worked on the simulation of the movement of substances in the extracellular space, with the help of professor Charles Nicholson and professor Hrabetova. Also, he has been developing a user-friendly graphical interface to allow people without programming knowledge to use the simulator. The software developed has a graphical interface to configurate a simulation (i.e. Fig 3) and a graphical interface that lets the user observe the diffusion process of substances and visualise the data of the experiments performed with the simulation.The software developed has a graphical interface to configurate a simulation (i.e. Fig 3) and a graphical interface that lets the user observe the diffusion process of substances (i.e. Figure 4) and visualise the data of the experiments performed with the simulation (i.e. Figure 5).
In addition to working on the HESSP project goals, Dr Miguel Tomé experienced an unexpected result during the project. While attending the Neural Systems course at SUNY Downstate, he generated a hypothesis about the functioning of the hippocampus for certain cognitive processes, and he is working on presenting this finding with Dr Juan M. Alarcon and Dr John Kubie.
During the second year of the project, Dr Miguel-Tomé worked on the simulation of the movement of substances in the extracellular space, with the help of professor Charles Nicholson and professor Hrabetova. Also, he has been developing a user-friendly graphical interface to allow people without programming knowledge to use the simulator. The software developed has a graphical interface to configurate a simulation (i.e. Fig 3) and a graphical interface that lets the user observe the diffusion process of substances and visualise the data of the experiments performed with the simulation.The software developed has a graphical interface to configurate a simulation (i.e. Fig 3) and a graphical interface that lets the user observe the diffusion process of substances (i.e. Figure 4) and visualise the data of the experiments performed with the simulation (i.e. Figure 5).
In addition to working on the HESSP project goals, Dr Miguel Tomé experienced an unexpected result during the project. While attending the Neural Systems course at SUNY Downstate, he generated a hypothesis about the functioning of the hippocampus for certain cognitive processes, and he is working on presenting this finding with Dr Juan M. Alarcon and Dr John Kubie.
The project will help us to better understand ES and to develop a new tool to examine the role of ES both in the nervous system and in the release of drugs. The software will help to improve our understanding of volume transmission, and the software architecture could be used in other scientific fields for systems that cannot be simulated in a direct way because of memory hardware requirements. Also, creating an algorithm to generate the anatomical geometry of nervous tissue is a current challenge, and it can even be considered its own field of research because few results exist on this topic in the current literature. Thus, the research in the HEPPS will help to for developing algorithms to achieve that issue.
The HAPS will be a tool to research the diffusion of substances, and a significant effort has been made to provide to the simulator with a graphical interface that makes it easy for researchers to use. It is hoped that this feature will attract the interest of researchers in the software being developed. The tool could help to researchers to make numerical predictions based on hypotheses about the extracelular space and the nervous tissue. It would also provide a proof of concept for the formulated simulation architecture that could be applied to other scientific fields.
For his secondment, Dr Miguel-Tomé has conceived an hypothesis about the function of the hippocampus and its role in human cognitive abilities. Exploiting this result requires meeting with other researchers who were not part of the initial project to explain and discuss the hypothesis with them and writing a scientific article. It will also require dissemination activities, but if the hypothesis is confirmed, it will impact the cognitive neuroscience open a new line of research in neuroscience and significantly benefit Dr Miguel-Tomé's research career.
The HAPS will be a tool to research the diffusion of substances, and a significant effort has been made to provide to the simulator with a graphical interface that makes it easy for researchers to use. It is hoped that this feature will attract the interest of researchers in the software being developed. The tool could help to researchers to make numerical predictions based on hypotheses about the extracelular space and the nervous tissue. It would also provide a proof of concept for the formulated simulation architecture that could be applied to other scientific fields.
For his secondment, Dr Miguel-Tomé has conceived an hypothesis about the function of the hippocampus and its role in human cognitive abilities. Exploiting this result requires meeting with other researchers who were not part of the initial project to explain and discuss the hypothesis with them and writing a scientific article. It will also require dissemination activities, but if the hypothesis is confirmed, it will impact the cognitive neuroscience open a new line of research in neuroscience and significantly benefit Dr Miguel-Tomé's research career.