The researchers utilized the diffusion MRI and neural tracer data of marmoset brains collected by the Brain/MINDS project to optimize the parameters of the algorithms for estimating whole-brain neural connections (connectome). The optimization allowed tracking of long-range fibers and raised an issue of parameter selection in connectomic studies.

Patients with 22q11.2 deletion syndrome (22q11.2DS) suffer from the onset risk for neuropsychiatric disorders over their lifetime. In this study, the researchers revealed “PRKR-Like Endoplasmic Reticulum Kinase-dependent vulnerabilities in dopaminergic neurons” as one of the molecular pathologies in brains of 22q11.2DS.

The researchers demonstrated that mimicking a de novo mutation of the schizophrenia-risk gene SETD1A in mice induced various abnormal behaviors relevant to schizophrenia. Setd1a in postsynaptic neurons positively regulates excitatory synaptic transmission and structure in the medial prefrontal cortex through histone modification and regulating the expression of diverse synaptic genes.

Direct and indirect pathway medium-sized spiny neurons (dMSNs and iMSNs) in the neostriatum were selectively labeled with green and red fluorescent proteins by an AAV vector. Both pathways formed two axonal arborizations in the globus pallidus external segment, and dMSN axons converged in the center of iMSN projection fields.

The researchers developed a simplified method for the production of AAV vectors, which drastically shortens the purification time from 1.5 days to 2 – 4 h. Systemic infusion of AAV-PHP.eB prepared using this method transduced whole brain. Transduction efficacy is comparable to the conventional method.