- Components of the hippocampus models (cells, microcircuit, region model) have been deployed in online use cases of the Brain Simulation Platform (BSP):
- online use case - single cells
- online use case - paired recordings
- online use case - in silico experiment on circuit
- online use case - validation
- An integrated workflow for single cell building and in silico experiments is available here.
- Recent publications are also available as live papers (interactive versions of the publication which enable one to download, visualise or simulate data, models and results presented in the publication): Here or here (in the BSP with additional functionality).
- Hippocampus datasets can be found in the Knowledge Graph at EBRAINS.
- Hippocampus models can be found in the Knowledge Graph at EBRAINS.
If you do not have an account to access the Brain Simulation Platform, please email email@example.com
A list of recent and relevant publications:
- Pousinha PA, Mouska X, Bianchi D, Temido-Ferreira M, Rajão-Saraiva J, . . . Marie, H (2019). The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding. Cell Reports.
- Martinello K, Giacalone E, Migliore M, Brown DA & Shah MM (2019). The subthreshold-active KV7 current regulates neurotransmission by limiting spike-induced Ca2+ influx in hippocampal mossy fiber synaptic terminals. Communications Biology.
- Economides G, Falk S & Mercer A (2018). Biocytin Recovery and 3D Reconstructions of Filled Hippocampal CA2 Interneurons. Journal of Visualized Experiments.
- Migliore R, Lupascu CA, Bologna LL, Romani A, Courcol J-D, … Migliore M (2018). The physiological variability of channel density in hippocampal CA1 pyramidal cells and interneurons explored using a unified data-driven modeling workflow. PLOS Computational Biology.
The hippocampus (wikipedia, scholarpedia) is a brain region that is known to play a key role in memory and spatial navigation, and is also heavily involved in brain disorders such as Alzheimer’s disease and epilepsy. Yet, despite intensive experimental and theoretical studies, the mechanisms through which the hippocampus contributes to these cognitive functions and dysfunctions are poorly understood.
What makes the hippocampus special?
The hippocampus is an evolutionarily conserved, old cortical region. Its structure is significantly simpler than that of the neocortex, but it is also in many ways (e.g. in terms of its main cell types) similar to other cortical areas, which makes it a popular target for experimental studies. Functionally, it is a high-level multimodal associational area linking many different types of information, and it is indispensable for remembering personal events (“episodes”) and is important for learning new facts. It also contains neurons that explicitly encode location in space (the so-called “place cells”); these are critical ingredients in the brain system responsible for navigation.
What was achieved in the HBP?
Over the last 6.5 years (October 2013-March 2020) we have:
- Generated data-driven models of CA1 microcircuits and full-scale networks (paper in preparation).
- Generated data-driven models of hippocampal synapses (paper in review).
- Demonstrated that the Kv7 current was active at rest in adult hippocampal mossy fibre synaptic terminals and enhanced their membrane conductance. This is a distinctive mechanism by which Kv7 channels influence hippocampal neuronal excitability and synaptic plasticity (Martinello et al., 2019); live paper
- Generated detailed models of hippocampal CA1 pyramidal cells and provided insight into two ion channel groups that have fundamentally different contributions to the cell’s behaviour (Migliore et al., 2018); live paper
- The validation suite for hippocampal neurons was extended with new tests and integrated with the validation framework developed for the Brain Simulation Platform.
- Established an efficient workflow for data-driven modelling of hippocampal neurons and circuits.
Building a model of hippocampus from sparse, fragmented data, and improving our understanding of hippocampal function, requires a critical mass of people and expertise, and can only be achieved in a collaborative manner.
The HBP Research Infrastructure Voucher Programme has been a way to develop and drive these collaborations. From 2019-2020, two vouchers were assigned to the Brain Simulation Platform team on two very interesting topics: 1) Tracking pre- and post-synaptic activity in the hippocampus and in the striatal complex in early and late stages of learning, and storage of spatial information, in collaboration with Andrea Mele (Center for Research in Neurobiology, Department of Biology and Biotechnology, University of Rome “Sapienza”, Italy) and 2) Building Alzheimer Disease Neuron Model, in collaboration with Hélène Marie (Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), CNRS, Valbonne, France).
Building and simulating a model of the hippocampus requires a critical mass of people and expertise. The following people and their teams are currently the main contributors of this effort:
Andrew Davison, Unité de Neuroscience, Information et Complexité, Centre National de la Recherche Scientifique, France
Audrey Mercer, University College London, United Kingdom
Michele Migliore, Institute of Biophysics, National Research Council, Italy
Armando Romani, Blue Brain Project, École Polytechnique Fédérale de Lausanne, Switzerland
Benefits to the Community
Model use: If you simply want to use some of the results of our work (e.g. take a CA1 pyramidal neuron for a spin, create your own variant thereof, analyse a CA1 network, etc.) you can go to the Brain Simulation Platform and launch one of the respective use cases. Alternatively, you can download data and models; they are made available upon publication of the relevant paper(s) and in the live papers. Please check the Resources section for details and links.
Participate in community modelling: We would be happy to hear from you. If you would like to get involved and contribute to our community effort, please contact any of us to discuss our common interests.