A new non-human primate model for translational brain research – Marmobrain

Thanks to their homology with humans at multiple levels, non-human primates are key animal models for investigating the neural underpinnings of brain functions in normal or pathological conditions. Over the last 5 years, the marmoset monkey model has quickly established itself as a worldwide new standard for brain research, spreading across nearly all fields in integrative neurosciences, from motor control to social interactions. Marmosets present several advantages when compared to non-human primates: they are small in size and easy to manipulate, they are easy to breed and their post-natal development is rapid. Finally, their brain is lissencephalic while keeping key features of the primate brain. To benefit from these advantages, new tools are proposed everyday, ranging from molecular engineering to neuronal recordings and behavioral exploration. However, the use of marmoset in the French neuroscience research system is rare and underdeveloped.

The objective of MarmoBrain is to kick-start the use of this new animal model in one of the top French laboratories in integrative neuroscience. Our ambition is to quickly catch-up in this highly competitive path, reinvesting our existing competences with primate and rodent models in multiple challenges grouped around in 3 scientific tasks. In TASK 1 (Phenotyping cognitive and social behaviors of marmosets in social groups) we aim at developing automated learning devices for marmosets to evaluate their performances in various cognitive and social tasks. Our goal is to phenotype social groups of marmosets that will be used subsequently for the functional explorations of TASKS 2 and 3. In TASK 2 (Multi-scale brain imaging of cortical networks in anesthetized and awake marmosets), we will explore in vivo the neural networks involved in visual and auditory processing at different scales. In particular we will transfer, master and customize imaging approaches for recording neuronal population activity at micro (two-photon imaging), meso (optical imaging and ECoG) and macro-scales (fMRI). Finally, in TASK 3 (Epigenetics of social and communication behaviors), we will explore how some specific miRNAs are involved in regulating prefrontal cortical networks involved in complex cognitive skills such as social behaviors. Here we plan to carry out a molecular screening to identify miRNA as potential modulators of precise social functions, and to develop AAV-based systems aimed at manipulating the expression of these miRNA in specific neuronal networks. These 3 tasks will be carried out and supervised by a strong consortium from partner 1 (INT) regrouping more than 100 person months and all the scientific expertise in behavioral control, brain imaging, electrophysiological recording, molecular and genetic tools to reach the project objectives. Additionally, the project will be supported by technical personnel from partner 2 (CEF2-Prim) for animal handling, husbandry, and surgeries.

This project is original and timely. Original as it aims at building a strong task force within a single research Institute to ignite brain research in marmoset monkeys while still focusing around complementary scientific challenges. At the end of Marmobrain, we envision the emergence of a reference center in France for this model part of the community of word-leading groups on this NHP model worldwide. Timely, because Marmobrain is the scientific counterpart of an unprecedented effort for structuring NHP research in basic and biomedical brain research on the site of Aix-Marseille University with the full support of the CNRS for a nationwide ambition. We strongly believe that supporting emerging and structuring scientific projects that aim at maintaining national competitiveness fit with the mission of the ANR Generic Call.