Building on the experience of creating wide-field two-photon microscopy that enables cellular-level observation of neural activities spanning different brain regions, innovative super-wide-field imaging techniques will be developed to monitor inter-regional neural activities. Moreover, multi-modal wide-field microscopy will be designed to observe individual neural activities and other biological signals simultaneously. These technologies will assist with the Core Organization and institutions involved in the Projects for the Priority Research Themes.

Genetically encoded fluorescent probes will be developed to monitor neural activities and their various effects at a range of spatial and temporal scales. Based on research regarding the interactions between light and matter, new bio-imaging techniques leveraging fluorescence and bioluminescence will be proposed. By using these techniques, imaging data will be collected from nonhuman primates and rodents, and their metadata will be standardized to optimize database performance. Moreover, fluorescence monitoring modalities will be developed to assist in structural analysis of postmortem human brains with and without neurodegenerative diseases.

Wild-type marmoset colonies will be maintained to provide marmoset models at the request of each researcher. Network cameras will be installed in the home cages of freely moving animals to monitor and record their natural behaviors. The recorded videos will be analyzed to detect the behaviors useful for their health assessment and care.

The breeding plans for the NCNP's wild-type marmoset colonies will be reorganized, taking note of the demands of participating institutions and supply schemes. Healthy marmosets will be produced and provided according to the breeding and supply plans over the 6-year course of this program. Moreover, to assist with the needs of this program, the NCNP's marmoset care and management database system will be modified, installed, and operated at the Core Organization and institutions involved in the Projects for the Priority Research Themes.

High quality magnetic resonance imaging (MRI) and large-scale analysis approaches applicable to both humans and nonhuman primates (NHP) will be explored to launch new technologies that precisely visualize wide-scale individual changes in brain biology. NHP brain data collected from macaques, marmosets, night monkeys will be standardized across species, preprocessed with high accuracy, and made publicly available through a database. International collaborations will be pursued to develop new cell-based transcriptomics and neuron-tracing techniques that facilitate multimodal data collection and creation of a common atlas template. Moreover, this group will assist the Core Organization and institutions involved in the Subprojects for the priority research themes with data collection, preprocessing and standardization.

We aim to integrate and analyze brain image data using advanced AI techniques. We will develop new algorithms for the integration of spatial gene expression data and for analyzing tracer signals. We will also develop AI tools for mapping between the marmoset and human brain space.

The brain developmental capacity and higher-order cognitive capabilities that humans and other primates have gained through evolution greatly differentiate them from mice and other rodents. These features of the primate brain are likely the result of genes that trigger primate-specific neural circuit formation. To understand the functional and structural developmental processes of the primate brain, the marmoset brain architecture will be investigated in detail using spatial transcriptomics and neuronal tracing.

This subproject will develop and operate an automated data processing platform capable of handling large volumes of raw data produced by animal laboratories. This platform will help build a user-friendly portal site that provides verified data on the global marmoset brain structure, and will operate it without interruption. Moreover, repository web sites will be created to facilitate data sharing between the organizations participating in this program.

Magnetic resonance imaging (MRI), a non-invasive imaging technique, is widely applied in clinical practice and research settings as an elemental technology for in-vivo brain imaging. Making full use of physical parameters of biological tissues (relaxation time, diffusion coefficient, susceptibility, magnetization transfer, chemical exchange saturation transfer, etc.) obtained by MRI, we will develop new measurement techniques that are applicable to human and animal and useful for detecting brain microstructures.

Viral vectors are an excellent gene transfer tool used in rodent, primate, and other experimental models. In particular, adeno-associated virus (AAV) vectors and lentiviral vectors are widely used to analyze brain structure and functions. These vectors are a promising gene delivery vehicle to create animal models of neurological disease. To accelerate the overall progress of this program, this group will construct and provide AAV or lentiviral vectors that serve the research needs of the participating scientists at their request.

In an effort to apply AI technology to biomedical research, a platform model that simulates the time course of marmoset behaviors will be created. Audiovisual recordings of these daily behaviors, three-dimensional computed tomography (CT) data on the anatomical brain structure, and genetic data will be collected and used to develop the model. Through machine learning, the model will learn to identify and simulate the complex and varied patterns of posture and behavior.