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.

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.

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.

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.

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.