One of the main goals of neuroscience is to understand the biological mechanisms responsible for human mental activity. In particular, the study of the cerebral cortex is and without any doubt will be the greatest challenge for science in the next centuries, since it represents the foundation of our humanity. In other words, the cerebral cortex is the structure whose activity is related to the capabilities that distinguish humans from other mammals. Thanks to the development and evolution of the cerebral cortex we are able to perform highly complex and specifically human tasks, such as writing a book, composing a symphony or developing technologies.
For these reasons the Blue Brain project emerged in 2005, when the L’Ecole Polytechnique Fédérale de Lausanne (Switzerland) and IBM jointly launched an ambitious project to create a functional brain model by means of reverse engineering of the mammalian brain, using the Blue Gene supercomputer from IBM. The aim was to understand the functioning and dysfunction of the brain through detailed simulations. By late 2006, the Blue Brain project had created a model of the basic functional unit of the brain, the neocortical column. However, the goals set by the project, which covered a period of 10 years, imposed its conversion into an international initiative (The Blue Brain Project, Nat Rev Neurosci. 7, 153-160, 2006). In this context, the Cajal Blue Brain project, the Spanish contribution to this international project, started in January 2009 led by the Universidad Politécnica de Madrid (UPM) and the Consejo Superior de Investigaciones Científicas (CSIC) .
Art and Technical Direction: Luis Pastor, Ángel Rodríguez, Susana Mata and Sofía Bayona - Art and Technical - Production and Development: Juan Pedro Brito and Luis Miguel Serrano - Technical Advice: José Miguel Espadero - Art Advice: Eva Cortés - Scientific Advice: Javier DeFelipe y Ruth Benavides-Piccione
"The garden of neurology offers the investigator captivating spectacles and incomparable artistic emotions. In it, my aesthetic instincts were at last full satisfied. Like the entomologist hunting for brightly colored butterflies, my attention was drawn to the flower garden of the gray matter that contained cells with delicate and elegant forms, the mysterious butterflies of the soul, the beating of whose wings may some day (who knows?) clarify the secret of mental life. […] Even from the aesthetic point of view, the nervous tissue contains the most charming attractions. In our parks is there any tree more elegant and luxurious than the Purkinje cell from the cerebellum or the psychic cell, that is the famous cerebral pyramid?"
Overall, the Blue Brain Project is based on the hypothesis of some scientists that detailed maps of the synaptic connections will be needed in order to understand how the brain functions. Such large-scale circuit reconstructions, “connectome and synaptome”, will soon be possible thanks to recent technological advances in the acquisition and processing of experimental data. Although the scientific community is divided on the feasibility and value of this working hypothesis, it is important to note that similar objections were voiced when the Human Genome Project was first proposed, now widely considered as a great scientific success.
One of the strengths of the Cajal Blue Brain project is that all the participating laboratories and research groups will be coordinated, so that all the effort will be channelled towards a specific objective, using strictly common methodological criteria. Thus, the data generated in a laboratory can be effectively used by other research groups. Definitively, the Cajal Blue Brain project is structured in such a way that it will work as a single, large multidisciplinary laboratory. In this way, the project will generate significant advances in our understanding of the structure and function of the normal brain.
The project is markedly interdisciplinary in nature, requiring the collaboration of scientists from different fields. The long-term objectives of the Cajal Blue Brain can be summarized as follows:
As the Universidad Politécnica did not have a Neuroscience laboratory equipped with the tools and personnel required to become a world leader in the research proposed through this ambitious project and other related projects, the joint UPM-CSIC "Laboratorio Cajal de Circuitos Corticales or LCCC (Cajal Cortical Circuit Laboratory)" was created, which is part of the Centro de Tecnología Biomédica or CTB (Biomedical Technology) of the UPM Montegancedo Campus. The work carried out at the LCCC, the maintenance of this laboratory and the progressive acquisition of the most advanced tools and technologies is essential in order to obtain the neurobiological data required to meet the project’s objectives. The maintenance of the LCCC is therefore a priority in the Cajal Blue Brain project as it generates the knowledge which is the basis for the subsequent development of computer tools and data analysis methods the project requires.
Since synapses are key elements in the structure of nervous circuits, understanding their location, size and proportion between the two different types is extraordinarily important in terms of function.
In this way, Espina tool automatically performs segmentation and 3D volume reconstruction of synapses in the cerebral cortex, helping the user to examine large tissue volumes and interactively validate the results provided by the software.
Morales J, Alonso-Nanclares L, Rodríguez J-R, DeFelipe J, Rodríguez Á and Merchán-Pérez Á (2011) ESPINA: a tool for the automated segmentation and counting of synapses in large stacks of electron microscopy images. Front. Neuroanat. 5:18. doi: 10.3389/fnana.2011.00018
ESPINA can display multiple spatially or temporally related images. These image sets are called stacks. The images that make up a stack are called sections. All the sections in a stack must be the same size and bit depth. ESPINA supports 8-bit images.
ESPINA is a memory intensive application. In a Linux x64 machine the maximum image stack size is only limited by the amount of RAM installed in the system (a machine with 4GB of RAM can process stacks up to 200MB in size). The Win32 version of ESPINA can only manage 2 GB of RAM and a maximum stack size of about 40MB. A Win64 version is currently under development.
Current understanding of the synaptic organization of the cerebral cortex depends to a large extent on knowledge of the synaptic inputs to the pyramidal cells. Indeed, their dendritic surfaces are covered by thin protrusions named dendritic spines, which represent the sites of most excitatory synapses in the cerebral cortex, and therefore, are critical in learning, memory and cognition.
This tool facilitates the analysis of the 3D structure of spine insertions in dendrites, providing insight on spine distribution patterns.
Juan Morales, Ruth Benavides-Piccione, Angel Rodríguez, Luis Pastor, Rafael Yuste, Javier De Felipe (2012). Three-Dimensional Analysis of Spiny Dendrites Using Straightening and Unrolling Transforms. Neuroinformatics October 2012 Volume 10, Issue 4, pp 391-407.
If you want to test the tool, we provide a test set you can use. Unzip it and load the file "api m16 1 5-1.spiral" from the Dispine dialogue "File->Open spines...".
We present a new method with musical feedback for exploring dendritic spine morphology and distribution patterns in pyramidal neurons. We demonstrate that audio analysis of spiny dendrites with apparently similar morphology may “sound” quite different, revealing anatomical substrates that are not apparent from simple visual inspection.
Pablo Toharia, Juan Morales, Octavio de Juan, Isabel Fernaud, Angel Rodríguez, Javier DeFelipe. Neuroinformatics, January 2014. Musical representation of dendritic spine distribution: a new exploratory tool
This tool presents a new technique for the generation of three-dimensional models for neuronal cells from the morphological information extracted through computed-aided tracing applications. The 3D polygonal meshes that approximate the cell membrane can be generated at different resolution levels, allowing balance to be reached between the complexity and the quality of the final model.
Neuronize implements a novel approach to generate a realistic 3D shape of the soma from the incomplete information stored in the digitally traced neuron using a physical deformation technique.
The addition of a set of spines along the dendrites completes the model, generating a final 3D neuronal cell suitable for its visualization in a wide range of 3D environments.
Brito JP, Mata S, Bayona S, Pastor L, Defelipe J, Benavides-Piccione R (2013). A tool for building realistic neuronal cell morphologies. Front Neuroanat. 2013 Jun 3;7:15. doi: 10.3389/fnana.2013.00015. eCollection 2013.
Neuronize requires Matlab Compiler Runtime 2012b (you can download freely, clicking on here)to be installed on your computer. Versions for Windows 32 and 64 bits platforms are available. Versions for Linux and Mac are under development.
The video may also help you see how to work with NEURONIZE. It shows a common working session:
Please register for release announcements and then proceed directly to download the NEURONIZE software.
The personal data you enter here will be stored and used for no other reason than to send you messages regarding NEURONIZE updates, bug fixes, and Cajal Blue Brain workshop announcements. Your data will only be disclosed to the entities directly involved with the development and release of NEURONIZE software.
We have developed an efficient computational technique to automatically extract the surface from synaptic junctions that have previously been three- dimensionally reconstructed from actual tissue samples imaged by automated FIB/SEM.
Juan Morales, Angel Rodríguez, José-Rodrigo Rodríguez, Javier DeFelipe and Angel Merchán-Pérez (2013). Characterization and extraction of the synaptic apposition surface for synaptic geometry analysis Front. Neuroanat., 04 July 2013 | doi: 10.3389/fnana.2013.00020
December 2013. The Human Brain Project.
June 2013. FET Flagship: Human Brain Project.
December 2012. 2012 Cajal Blue Brain Project.
June 2012. Restructuring of the Cajal Blue Brain Project.
December 2011. Alzheimer 3n.
June 2011. The Human Brain Project-Preparatory Study.
December 2010. Cajal Blue Brain in Science.
June 2010. Cajal Blue Brain Project on media.
December 2009. First Year of th Project.
June 2009. The Launching of the project.
The Cajal Blue Brain project is managed and developed almost entirely at the Polytechnic University of Madrid (UPM), Campus Montegancedo. Researchers and engineers are located in two locations, the Center for Biomedical Technology (CTB) and the Supercomputing and Visualization Center of Madrid (CeSViMa), CTB being the headquarters project.
If you are interested in the project and / or wish to have more information about it, they can get through social networks, VCard, QR code, or the contact form shown below: