Core Institute (RIKEN)
Structure and functional mapping of the non-human primate brain
Structural and functional mapping of marmoset neural circuitry using an ultra high field MRI machine, and generation of genetically-modified marmosets
The Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) Project aims for both structural and functional brain mapping of the common marmoset. Marmoset brain functions are relatively close to those of humans, and transgenic approaches can be applied to them. The Laboratory for Marmoset Neural Architecture works on macro-level structural and functional mapping of marmoset neural circuitry using an ultra high field MRI machine. The laboratory also aims to generate disease model marmosets and genetically-modified marmosets that are useful for brain mapping and brain disease research.
Future extraction of neural circuits underlying the marmoset prefrontal cortex
We are going to analyze the global neural networks and hope to identify the entire neural connections at a mesoscopic level in the marmoset prefrontal cortex. Towards this goal, we are currently developing the tools for retrograde vector, AAV vectors, two photon imaging systems in combination with cell type specific transgenic techniques.
Functional and structural mapping of primate brain from macroscopic to microscopic level by multidisciplinary methods and function-structure linking of primate cerebral cortex
After mapping function of the cortical area by physiological methods, using histological and hodological methods, the homological areas in other primate will be identified. Then, from these areas, using tracers as well as histology, other areas will be determined. These areas and connectional tracts will be matched to MRI-based areas and fiber-tracts by DTI. Each cortical areas have specific layer-based neural construction and myelination. In each area, layer specific functional intra-areal and outer-areal connection will be elucidated by methods using laser in in vitro preparation. In in vivo preparation, using 2 photon-microscopy, functional mapping of primate cortex in one cell level will be examined. By integration of these experiment, how cortical neurons function will be modeled.
Comprehensive gene expression analysis in neonate marmoset brain
Our goal is to find molecular mechanisms which control specie specific brain function. To achieve this, we first use common marmoset brain to perform comprehensive gene expression analysis and next perform comparative expression analysis with mouse brain. Our results provide useful molecular toolbox to reveal brain evolution.
Neural Mechanisms Subserving Marmoset Social Behaviors
Replacing previous neuroscience paradigm of testing hypothesized individual subject/animal’s cognitive functions, we aim to detect neural mechanisms subserving complex social interactions emerging among multiple individuals. This represents novel paradigm of “exploratory analysis of interactive neural circuits with long-term changes along development of complex cognitive behaviors”, using marmosets that share some common social behavioral features with humans. Based on these, we try to establish novel algorithms to evaluate dynamics of behavioral pattern transitions over long time and to identify neural mechanisms subserving these behavioral changes. In addition, we will build a general-purpose automated system to efficiently evaluate the effect of neuropharmacological, genetic, or other experimental manipulations, whereby establish a standardized pipeline for evaluation of such marmosets produced by partner laboratories.
Generation of the 1st non-human primate model of Alzheimer’s disease
We will work together with Hideyuki Okano Team (Keio & RIKEN) and Erika Sasaki Team (CIEA, RIKEN & Keio) to generate the 1st non-human primate model of Alzheimer’s disease (AD). Right now, experimental research of AD utilizes mouse models because they are easy to handle and to breed. The mouse models, however, differ from humans biologically, for instance, in the immune system and in cognition and thus may cause, at least in some cases, a failure in preclinical trials of medication candidates. So, non-human primate models could improve preclinical trials and may also contribute to elucidating the mechanism(s) underlying the transition of Aβ amyloidosis to tauopathy and neurodegeneration.
Molecular and functional architecture imaging in marmoset brain
To clarify the relationship between molecular and functional network in the brain and the pathology or social behavior, we will perform fusion analysis of functional network image by fMRI and neurotransmission image by PET, and will establish the method for quantitative molecular and functional architecture imaging. By analyzing a variety of disease model marmosets, which were varied with specific neural networks and neurotransmission function by drug administration or genetic modification, we will extract the “imaging biomarkers” which are translatable to human psychiatric and neurological disorders as “intermediate phenotype”.
A Mesoscale Circuit Map of the Marmoset Brain
The goal to obtain a mesoscale circuit map of the brain of the Marmoset, using injections of neuronal tracer substances placed on a systematic grid designed to cover one hemisphere of the brain. Both viral and classical tracer substances, transporting in anterograde and retrograde directions, will be used to map the inputs/outputs of brain regions. The brains will be processed in a high throughput neurohistology pipeline, producing a collection of whole-brain digital light microscopic data sets. The raw data will be made publicly available through a data portal, as well as subjected to computational neuroanatomical analysis, to obtain a mesoscale circuit map of the Marmoset brain. This sub-component of the Brain/MINDS initiative is an international collaborative effort centered at Riken BSI.
Development of novel, cutting-edge technologies that support brain mapping
Imaging brain functions in action
In the nervous system, on the one hand, intracellular signaling events are closely linked with electrical activities and play essential roles in information processing. To identify and characterize the mechanisms by which signals are organized inside cells, it is necessary to analyze spatiotemporal patterns of signaling pathways. On the other hand, neural circuitry operates as an ensemble in the nervous system. To investigate the patterns of neuronal firing, it is necessary to monitor multiple transmembrane voltages or signals that result from electrical activity in complex tissues or intact animals. Over the past decade, various probes have been generated principally using fluorescent proteins. We are developing novel probes that will advance our understanding of the spatio-temporal regulation of biological functions inside neurons and brains. We also aim at in-depth brain imaging, which is one of the most sought-after themes of today’s optical technologies; we have been and will be engaged in the development of new technologies that would advance the imaging depth limit.
Developing novel MRI techniques for comparative studies of human and non-human primate brains
This project aims to develop novel MRI techniques for comparative studies between human and non-human primate brains. The emphases are on imaging the entire human brain with high temporal and spatial resolutions. In particular, we will 1) implement and assess the multi-band imaging method that covers the entire brain with the sub-millimeter resolution in a couple of seconds, 2) devise the parallel transmit capability that mitigates the problem of signal dropouts due to the susceptibility artifact in inferotemporal and orbitofrontal cortices, and 3) develop a multi-shot high-resolution diffusion tensor imaging (DTI) method for detailed connective analysis of brain networks.
Mechanisms controlling the variability of synaptic strengths in defined synaptic circuits
Synapses are essential nodes of information transmission in the brain, and dynamic changes in the efficacy of synaptic transmission play a fundamental role in cognitive functions including emotion, computation, perception and learning and memory. Our research seeks to understand how individual synapses acquire a particular strength, and how the strength of individual synapses is dynamically modified by network activity and in relationship to other synapses sharing the network.
Developing Multi-scale Data Analysis Tools and Modeling of Large-scale Neural Network / A Theoretical Approach to Brain State Characterization
Advances in recording technologies have enabled the acquisition of neural activity at unprecedented scale and resolution. Developing data analysis tools and models is critical for us to make sense of these data. In this project, we take a dynamical systems approach to develop such tools and investigate how the dynamical state of the brain is shaped by neural circuits and the environment.
Development of combined techniques of optogenetics and large-scale electrophysiology recording in deep brain areas
In this project, we aim to develop combined techniques of high-density large-scale electrophysiology recordings and optogenetical manipulations, for enabling observations of simultaneous neuronal firing activities and interactions of large amount of neurons in various brain areas, including deep brain regions, in freely behaving animals such as rats and marmosets.
Development of new microscopes to monitor a large number of neurons
It is likely that brain functions are expressed by cooperative activity between highly specialized brain areas. To understand the mutual interaction, we try to develop new microscopes to monitor a large number of neurons form a large field of view or from multiple areas at the same time. Questions to be answered are how neural activities propagate; what kind of neurons support these activities; when, where and how the activities go on; and whether these activities depend on animal behaviors.
Developing Multi-scale Data Analysis Tools and Modeling of Large-scale Neural Networks
Mathematical Tools for Data-driven Neural Circuit Modeling
Recent advances in recording technologies are making it feasible to simultaneously record the activity of hundreds and thousands of neurons from behaving animals. However, methods to analyze the activity data of a large neural population are still to be developed. In this project, we develop mathematical technologies to uncover the spatiotemporal characteristics of neural population activity to read neural code and to model the circuit mechanisms underlying various brain functions.
Development of Neuroinformatics Infrastructure for the Database and Data analyses
We aim to develop neuroinformatics infrastructure for the database and data analyses which enable the reuse of the research data in open access, Mission in the initial stage is the development of database servers for heterogeneous big data and designing digital brain atlas for multiple brain imaging data.
Image Processing Research Team, Extreme Photonics Research Group, Center for Advanced Photonics
Multi-dimensional brain image processing research
The team is devoted to develop new and efficient image processing techniques for brain science. In this project, the image information of the ultra-large-scale is produced every day. For this subject, we promote the image processing research on recognizing image segmentation method automatically nerve cells. For this purpose, we will research and develop new techniques related to machine learning and expert system for large-scale data. By building a system, we reproduce cognitive identification of a human on the computer, and to contribute to brain function analysis.