Brain Mapping by Integrated Neurotechnologies for Disease Studies

Studying the neural networks controlling higher brain functions in the marmoset, to gain new insights into information processing and diseases of the human brain.

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Multi-scale light microscopy/electron microscopy neuronal imaging from brain to synapse with a tissue clearing method, ScaleSF

The researchers have extended the applicability of tissue clearing techniques to EM. For this, they developed an ultrastructurally-preserved tissue clearing method, ScaleSF, and LM/EM dual labeling stable in the clearing protocol. Their imaging pipeline allows for deciphering brain-wide connectivity by simultaneous interrogation of the neural circuit structure and synaptic connectivity.


Distributed sensory coding by cerebellar complex spikes in units of cortical segments

With a fluorescence calcium sensor yellow cameleon, the researchers succeeded in measuring complex spike activity in over 20,000 Purkinje cells simultaneously in the mouse cerebellum. The results have shown that combining activity patterns in "olivocerebellar segments" as a whole performs distributed population coding, which represents sensory input in real-time.


Somatostatin-evoked Aβ catabolism in the brain: Mechanistic involvement of α-endosulfine-KATP channel pathway

The researchers identified a novel mechanism, by which amyloid β peptide (Aβ), a primary cause of Alzheimer’s disease (AD), is degraded in brain. This mechanism can be modified by diazoxide, a medication used to treat low blood sugar, implying a potential application of this mechanism to prevention and treatment of AD.


A genetically targeted reporter for PET imaging of deep neuronal circuits in mammalian brains

The researchers established a new method for PET imaging of the expression, chemogenetic manipulation, and intermolecular interaction of reporter proteins in the neural circuit of living animals. This technique may facilitate a broad spectrum of PET analyses of a mammalian brain circuit at molecular levels that were not previously applicable for technical reasons.


Functional and molecular characterization of a non-human primate model of autism spectrum disorder shows similarity with the human disease

In the cortex of a marmoset model of autism exposed to valproic acid in utero, genes associated with neurons and oligodendrocytes were down-regulated, and genes associated with microglia and astrocytes were up-regulated, as in human autism. However, the current major rodent models could only reproduce human autism in at most two of the four cell types of the brain. This confirms the prediction that primate autism models reproduce human autism better than rodent models by an objective method of transcriptome comparison.


Current Status of and Perspectives on the Application of Marmosets in Neurobiology

The common marmoset (Callithrix jacchus), a small New World primate, is receiving substantial attention in the neuroscience and biomedical science fields because its anatomical features, functional and behavioral characteristics, and reproductive features and its amenability to available genetic modification technologies make it an attractive experimental subject. This review outlines the progress of marmoset neuroscience research and summarizes both the current status (opportunities and limitations) of and the future perspectives on the application of marmosets in neuroscience and disease modeling.


A third-generation mouse model of Alzheimer's disease shows early and increased cored plaque pathology composed of wild-type human amyloid β peptide

The researchers generated a new Alzheimer’s disease (AD) mouse model that more faithfully recapitulate pathology of AD patients compared to the previous ones. This new third-generation mouse model will help accelerate the elucidation of the disease mechanisms and development of disease-modifying therapies to treat AD.


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Related Projects

  • International Brain Initiative
  • Marmoset Gene Atlas
  • Brain/MINDS Data Portal

Supported by

Japan Agency for Medical Research and Development