Brain Mapping by Integrated Neurotechnologies for Disease Studies

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Mission and Objectives

One of the important characteristics of Brain/MINDS will be that we pay considerable efforts in the mapping the brains of a small new world monkey, the common marmoset (Callithrix jacchus), since research on the non-human primate brain is essential for understanding the human brain and for developing knowledge-based strategies for the diagnosis and treatment of psychiatric and neurological disorders. Furthermore, common marmoset has the following advantages for brain mapping; i) Its frontal lobe is more developed than in other commonly used animals – more similar to humans; ii) The brain is compact (approximately 8 grams) and is suitable for comprehensive analysis of the neural circuit. iii) Marmosets can be genetically modified and manipulated. The objectives of Brain/MINDS can be categorized into the following three major groups (A~C):

Structure and functional mapping of the non-human primate brain (particularly the marmoset brain): In the Group A, as regards the structural (anatomical) mapping of the common marmoset, we will examine macroscale, mesoscale and microscale mappings by utilizing MRI-based diffusion tensor imaging (DTI), sterotactic tracer injections followed by light microscopic observations and A new method of serial EM (developed by Prof. Jeffery Lichtman at Harvard University), respectively. Transgenic techniques of common marmoset would contribute to mesoscale mapping in a cell-type specific approach. We will examine the functional mapping of the marmoset brain by resting state fMRI. As outputs of brain functions, behavioral and cognitive test batteries of common marmoset will be established.

Development of novel, cutting-edge technologies that support brain mapping: In the Group B, B1) High-resolution, wide-field, deep, fast and long imaging techniques for brain structures and functions, B2) Development of new techniques for controlling neural activity, and B3) Development of neuroinformatics for integrating heterogeneous and multi-scale data will be investigated. In B3, we are planning to cooperate with INCF, HBP and Allen Institute for Brain Science for generating database in the common formats.

Human brain mapping and clinical research: Here, we aim to map control and patients-derived human brains. In the Group C, three clinical research teams will be organized, including Neurodegenerative Disease Research Team, Psychiatry Disease Research Team and Vascular and Neuro-rehabilitation Research Team. These clinical research teams will generate multi-center patients-derived database of MRI and other biomarkers and will make feedbacks to marmoset researches.

Reciprocal translation among the Groups A, B, C will be examined to determine causal relationships between the structural/ functional damage of neuronal circuits and disease phenotypes and to eventually develop innovative therapeutic interventions for these diseases. It is obvious that extensive international collaboration will be required to achieve the goals of the project.