The Co-Design Projects (CDPs) have been chosen for their feasibility and potential value to different groups of target users. Working within and across Subprojects, each CDP aims to deliver a number of infrastructure product advances, which are a set of functionalities to achieve cross-Platform bridges and workflows in line with the objectives of the HBP. The CDPs are intended to drive these cross-Platform developments, involving tasks and investigators from both Neuroscience and Platform SPs, towards the realisation of an aligned Research Infrastructure. The HBP anticipates that the delivery of these products will generate new insights in neuroscience, medicine and computing.
Co-Design Project 1
Co-Design Project 1 -
Development of the Whole Mouse Brain Model and the Related Mouse Brain Atlas
The first of the HBP Co-Design Projects, which involve multidisciplinary units from a number of Subprojects, consists of two components focused on research and engineering.
The first of these focuses on defining a number of scenarios (‘use cases') that represent some of the larger scientific questions that can be addressed using the HBP Platforms once the Co-Design Project has been completed. These research use cases will define which in silico preparations (e.g. whole brain models, slice models, etc.) the Platforms should provide, and how they can be measured and stimulated. The use cases also define the types of signals that can be measured in the in silico preparations, which will, in turn, dictate the granularity of the models (e.g. population/field models, point neuron networks, etc.) that should be used. The engineering component of the Co-Design Project will focus on developing Products based on the HBP Platforms that will make the use cases possible. For each of these Products, the researcher should be able to formulate the use case or related experiments in the Collaboratory, run the experiment in the Collaboratory, and access and analyse the results of the experiment in the Collaboratory or offline. A physical experimental platform will also be provided, to generate key missing mouse brain data to refine and validate the simulations.
The CDP1 Products are as follows:
- CDP1-P1: Reference set-up of the experiment
- CDP1-P2: A virtual anatomy lab app
- CDP1-P3: A virtual imaging lab app
- CDP1-P4: A virtual behaviour lab app
- CDP1-P5: A data explorer and importer app
CDP Science Leader: Francesco PAVONE
CDP Implementation Leader: Marc-Oliver GEWALTIG
Co-Design Project 2
Co-Design Project 2 -
Mouse-Based Cellular Cortical and Sub-Cortical Microcircuit Models
CDP2 will integrate the activity of HBP platforms in order to refine brain modelling tools through their interactive use open to an enlarged scientific community.
This will happen in two steps, first by exploiting the intrinsic capabilities of HBP teams and then by involving external laboratories as well. CDP2 will build on the experience of the microcircuit model of the somatosensory cortex that has been developed by the EPFL's Blue Brain Project. This requires 3D reconstructions of different morphological types of neurons, with connectivity constrained by published data and facilitated using axonal reconstructions where available. The workflow uses the optimiser framework for the electrophysiological properties of the different neuronal types (e-types). The same strategies and workflows are currently used to develop a draft model of the hippocampal region, which will be used as a benchmark for community development. Similar strategies are currently being investigated for non-cortical regions such as the cerebellum and the basal ganglia. In these cases, model development will first be driven by HBP groups, since the specific features of these brain regions may require adaptations to the general workflow. The transversal SPs activities being performed by this project are highly relevant to the microcircuit models that are being developed, as this modelling work lays the foundation for data-driven modelling of neuromodulation, synaptic plasticity, in silico experimentation, and robotics. This approach also provides a bridge to systems biology and may be instrumental for future HBP drug discovery efforts.
The Products to be developed by CDP2 are as follows:
- CDP2-P1: Hodgkin-Huxley neuron builder
- CDP2-P2: Single model benchmark and validation suite
- CDP2-P3: Community-based modelling strategy on the example of cellular-level hippocampus model
- CDP2-P4: Cellular-level basal ganglia model: generalisation strategies
- CDP2-P5: Cellular-level cerebellar model: generalisation strategies and integration in robotic systems
- CDP2-P6: In silico experimentation lab on the example of the cellular-level neocortical model
CDP Science Leader: Egidio D'ANGELO
CDP Implementation Leader: Michele MIGLIORE
Co-Design Project 3
Co-Design Project 3 -
Multi-Level Human Brain Atlas
The overall aim of Co-Design Project 3 is to develop a prototype of a comprehensive multimodal and multi-scale human brain atlas.
To support this, CDP3 will develop eight Products, which depend on components in several Tasks in different Subprojects. Most of the Products depend on a mixture of Tasks in several Subprojects, including SP2 (Strategic Human Brain Data), SP4 (Theoretical Neuroscience), SP5 (Neuroinformatics), SP7 (High Performance Analytics and Computing), SP8 (Medical Informatics) and SP12 (Ethics and Society). Since all of the CDPs focus on developing relevant and usable parts of the overall infrastructure that are highly scientifically relevant within the scope of SGA1, prioritisation and selection of the initial Atlas Products is required. The initial work of CDP3 in SGA1 will be the construction of a topographical representation of the human brain on different scales and considering different aspects, followed by a comprehensive semantic representation in future SGAs. The selection of Products under SGA1 is based on the following principles:
- Products with a clearly defined use case, with practical relevance beyond the HBP
- Data sets to finalise the Product must be available in 2015, so that subsequent work in SGA1 can focus on integration of the data into the Neuroinformatics Platform
- Products should be based on 2D or 3D image data sets that could be topographically integrated into an agreed template.
The CDP3 Products to be developed are as follows:
- CDP3-P1: 2D interactive filmstrip viewer
- CDP3-P2: 3D interactive big data viewer
- CDP3-P3: Initial set of linked template data sets with labelled parcellations
- CDP3-P4: Initial qualitative and quantitative data sets
- CDP3-P5: Alignment tools for incoming data
- CDP3-P6: Initial set of interactive tools
- CDP3-P7: Realignment of knowledge graph for inter-subject variability
- CDP3-P8: Modelling and model validation using quantitative data
CDP Science Leader: Katrin AMUNTS
CDP Implementation Leader: Timo DICKSCHEID
Co-Design Project 4
Co-Design Project 4 -
The overall aim of Co-Design Project 4 is to develop and implement multi-modal, neurobiologically realistic models of sensorimotor integration, to include advanced object recognition and spatial localisation tasks to guide robotic motor control.
To do this, the CDP will use a top-down modelling approach to translate conceptual models into computational architectures and ultimately into spiking neuronal network models that both use the HBP Research Infrastructure and contribute to its co-development.
CDP4 will initially focus on visuo-motor integration, which will include modelling of the attention-for-action tasks that are required to obtain parameter specifications for motor execution. This will integrate ongoing work from SP2 (Strategic Human Brain data) and work from SP3 (Cognitive Architectures) on realistic models of invariant object recognition and the role of attentional selection for both object recognition (ventral processing stream) and motor planning/spatial awareness (dorsal processing stream). These models are empirically constrained and will be combined with bottom-up simulations developed in collaboration with SP4 (Theoretical Neuroscience), SP6 (Brain Simulation) and SP7 (High Performance Analytics and Computing); these will lead to empirically validated computational architectures of visuo-motor integration. In later stages of the HBP, the models will be extended to other sensory modalities, focusing on the somatosensory and auditory systems. The sensorimotor modelling will be integrated with the development of algorithms for multi-modal guidance of robotic motor control with feedback (somatosensory) and feed-forward (visual and auditory) loops, in collaboration with SP10 (Neurorobotics).
The combined efforts of the CDP4 group could lead to an HBP showcase of neuroscience observations implemented in the HBP Research Infrastructure. This could demonstrate to the scientific community the exciting work that cuts across the entire Project and helps to integrate the work of different SPs. For example, CDP4 may show how visual and somatosensory information is integrated in the human brain to continuously adjust motor control during complex tasks such as writing or using a scalpel. By establishing a human brain atlas at ultra-high resolution, and unravelling the corresponding computational circuits by large-scale simulations, we can incrementally develop a truly comprehensive visuo-motor and somatosensory brain model of complex motor control. Subsequently translating such models to neurorobotic applications can provide an end product that can have real-world applications, such as robotic surgery systems.
The CDP4 Products to be developed are as follows:
- CDP4-P1: Neural sensorimotor integration network
- CDP4-P2: Large-scale models on sensorimotor integration
- CDP4-P3: Spiking neuron models for sensorimotor integration
- CDP4-P4: Neurorobotic closed-loop engine
CDP Science Leader: Rainer GOEBEL
CDP Implementation Leader: Sonja GRÜN
Co-Design Project 5
Co-Design Project 5 -
Functional Plasticity for Learning in large-Scale Systems
Co-Design Project 5 is targeting learning the phenomenon of learning, providing a link between the transfer of biological learning principles (explored in the Brain Simulation (SP6) and Neuromorphic Computing (SP9) Subprojects) and the Neurorobotics Platform.
It also offers a connection between biological neuroscience data and Cognitive Neuroscience (SP3), strongly guided by Theoretical Neiroscience (SP4) and with a solid foundation in the biology of learning and plasticity investigated in SP3, but also in SP1 (Strategic Mouse Brain Data) and SP2 (Strategic Human Brain Data). Diverse biological data on synaptic plasticity will also need to be integrated and the functionality of learning transposed to the Platforms.
Synaptic plasticity as the basis for learning and development is particularly challenging, since the time taken for developmental and learning processes ranges from milliseconds (for neuronal action potentials) to days (for behavioural learning paradigms) to several years. Simulations of these processes therefore need to recreate this, and can only be realistic if it as fast as, or preferably significantly faster, than the biological time taken. The Neuromorphic Platform, which offers an accelerated time factor of several thousand, is therefore ideal to test these paradigms.
The outputs developed in CDP5 will provide scientific guidance for designing the neuromorphic hardware systems and providing them with the capability of learning. Such systems will be an incredibly useful tool for future users when designed in iterative cycles between neuroscientists and engineers. This therefore requires very close collaboration between experimental neuroscientists, theoreticians and engineers from the various Subprojects, and the Products to be developed within CDP5 will support this.
These Products are:
- CDP5-P1: Suite of benchmark learning tasks
- CDP5-P2: cellular and cognitive determinants of functional plasticity
- CDP5-P3: Guiding platform design on functional plasticity
- CDP5-P4: Concept showcases in big systems
CDP Science Leader: Walter SENN
CDP Implementation Leader: David LESTER
Co-Design Project 6
Co-Design Project 6 -
Modelling Drug Discovery
Any innovative approaches to brain diseases require a detailed understanding of the causes of the diseases at all levels of organisation from the molecular to the cognitive & system levels, as well as disease progression and response to treatment.
These issues are particularly challenging for neurological and psychiatric diseases due to the extreme complexity of the nervous system. At this stage, no efficient curative treatments yet exist for neurodegenerative diseases such as Alzheimer's and Parkinson's, despite large research investments.
The search for new drugs for brain diseases is considered an ethical priority for neuroscience research, and the HBP is in a unique position to contribute to it. In particular, this will be through better definitions and diagnoses of the diseases with the generation and organisation of large sets of data, and mostly through the ability to simulate the responses in the brain to various influences, ranging from drug administration, environmental care, to gene mutations. The aim of CDP6 is, ultimately, to coordinate research efforts to establish new protocols to increase the efficiency and speed of the drug discovery process, thereby enhancing innovation at lower costs. Several areas of research have been identified that are of particular interest for the drug design programmes, They include ligand-gated and G-protein linked receptors and their allosteric properties, diversity of receptor distribution in the brain, glial cell metabolism, and physiological and drug-elicited synaptic plasticity. Functional models of signalling and metabolic pathways, from which drug discovery targets may be elucidated, may be provided through data integration and analysis and simulations at the atomic, molecular and cellular levels.
This obviously requires a significant research investment. CDP6 therefore intends to build on the HBP Research Infrastructure for data collection and analysis, and to complement HBP funding to seek external funding from national and private agencies, in particular pharmaceutical companies. Importantly, all of the proposed simulations will be performed on the High Performance Analytics and Computing Platform (HPAC) from HBP, and will therefore benefit from close collaboration with Subproject 7. CDP6 will demonstrate the key role of HPAC-based simulations in the design of new classes of drugs targeting the multiplicity of allosteric sites carried by the receptor proteins in the course of their conformational transitions.
The CDP6 Products to be developed are as follows:
- CDP6-P1: Modelling receptor allostery
- CDP6-P2: Pharmacological modulation of synaptic plasticity and drug design
- CDP6-P4: Ethical implications of drug design
CDP Science Leader: Jean-Pierre CHANGEUX
CDP Implementation Leader: Paolo CARLONI