Enhanced mouse atlas for cerebellar connectivity

Project Summary

ATLAScer captures a fundamental point for the reconstruction of the connectome in whole- brain models. Indeed, while MRI tractography does not resolve synaptic relays in multi-synaptic pathways or fibre directionality, this can be done using viral tracing and fluorescent axon imaging in rodent preparations. Since in SGA3 there will be an open call on rodent brain modelling, this work proposed by ATLAScer will be essential to the purpose. An enhanced connectome will be generated for the cerebello-cerebrocortical loops. The project is grounded on solid scientific basis and on the unequalled experience of the Allen Institute. The HBP partners are leading in the development of rodent brain models (UNIPV) and are also working on the corresponding physiological exploration of cerebello-cerebrocortical pathways. UNIPV is currently responsible for applications on the HBP modelling infrastructure for whole-brain modelling (BSP). The work plan consists of specific actions that can be scheduled as follows:

a. investigate / refine the mouse cerebellar connectivity. Curate and improve the connections available on the Allen Mouse Brain Atlas in order to define the cerebellar inputs, cerebellar outputs, and the connections of deep cerebellar nuclei. The main points are to determine / define multi-synaptic pathways from tracing data based on single synaptic relays, to maintain somatotopic representations, and to correlate the pathways to modular representations compatible with anatomo-physiological knowledge and TVB architecture.

b. update the Allen Mouse Brain Atlas and make it available for uploading into the mouse brain model of HBP in EBRAINS and The Virtual Mouse Brain (TVMB).

c. set-up the connectome in the mouse brain model on EBRAINS and verify its functionality through simulations of stimulus-response protocols. We believe the project will be feasible in 12 months.

We estimate that this project will be feasible by enrolling an experienced researcher for 12 M in the HBP partner research units. The refinement and enrichment of the connectome, its integration into platforms and its functional testing will require 12 PM by UNIPV with a programmed secondment to ALLEN for the months required. The integration of the connectome into EBRAINS will be performed by UNIPV.

The ATLAScer connectome is a component that will be integrated into the Brain Reference Framework and further used in pyNEURON, pyNEST (and possibly ARBOR, depending on its stage of development) and TVB/TVMB. ALLEN is a well structured institute with long-term programs for data maintenance. UNIPV has been listed among the European Hubs for model development and integration that will exist beyond HBP and continue its activity. TVB/TVMB will be maintained by AMU.

Contribution to the HBP

The integration of ALLEN connectomes into the Brain Reference Framework is a long-term plan of the Human Brain Project and therefore ATLAScer is fully relevant and perfectly fits into this scheme. The mouse brain model has been recognized as a critical element for the HBP development and has been attributed an open call in SGA3. An enhanced connectome is much needed in order to validate fundamental constructive hypothesis of the whole-brain models and will reverberate onto the human brain models allowing the validation of their constructive principles. There are specific tasks in WP4 for the integration of ALLEN atlases. This project therefore identifies a critical missing element and provides a direct answer to fix it. We believe this project will give a critical contribution to the Research Infrastructure-related Objectives.

This development is very much needed, as it is the missing link between brain connectivity and brain activity in detailed whole-brain models. The reconstruction of brain models using EBRAINS and TVB – pyNEST cosimulations would be severely limited in the absence of this enhanced atlas.

This enhanced ATLAS will allow to make reliable predictions about the structure-function relationship in whole-brain models. This is an issue elaborated in the most important laboratories world-wide and therefore the list of potential users is remarkable. It includes all of those who are interested in brain mechanisms, brain models, brain functions, structure-function relationships. There is currently no comparable ATLAS available. We therefore believe the attractiveness will be quite high with users through both EBRAINS, ALLEN, TMVB.

Finally, it is important to notice that this proposal comes from an influential non-European laboratory (USA), the Allen Institute, already deeply integrated with the Human Brain Project atlasing system. This aspect is of the highest relevance to foster the diffusion of Human Brain Project activities worldwide.

At this stage of development, the innovation potential of the work will be focused on the scientific domain. However, given the maturity of the model, exploitation can be expected not only in terms of scientific publications but also for applications to the robotic industries. This latter aspect however, would require additional resources for specific in situ dissemination activities targeting the possible industrial partners, to better illustrate the model, the results, and the possible commercial application.

Key facts

Time frame: 2020-2023

Origin: Voucher programme