We confirmed, for the first time, that Lewy bodies contained amyloid fibrils using autopsied brains of Parkinson's disease patients. Collaborative research with the large-scale synchrotron radiation facility, SPring-8, enabled ultrastructural analysis of aggregates in brain sections. These new findings are expected to be applied to the development of diagnostic and therapeutic approaches for Parkinson's disease.
A new protein involved in Alzheimer’s disease (AD) has been identified by researchers at the RIKEN Center for Brain Science (CBS). CAPON may facilitate the connection between the two most well-known AD culprits, amyloid plaques and tau pathology, whose interactions cause brain cell death and symptoms of dementia. This latest finding from the Takaomi Saido group at RIKEN CBS uses a novel mouse model of AD.
The study was published in Nature Communications on June 3.
We here developed a multicolor GECI suite, "XCaMP", which enables to image high-frequency firing patterns, non-invasively measure hippocampal CA1 dynamics, and simultaneously record pre- and postsynaptic firing, or co-image neuronal activities in 4 distinct celltypes. XCaMPs will be useful for elucidating complex brain circuit dynamics in health and neuropsychiatric diseases.
Human, who has cooperative society, can tell who has reciprocity and who does not, by observing others' interaction. This study showed that highly prosocial common marmosets have this ability, but despotic Japanese monkeys do not. These results suggest that common marmoset is a suitable animal model for studying human social disorder, such as autism.
In the neonatal autism-model marmoset, we showed a significant reduction of anterior commissure, which connected bilateral social brains. Abnormal expression of axon guidance molecules mediating formation of anterior commissure were also observed in this animal-model. These features might be useful for early diagnosis and early intervention/ therapy of human autism.
The Brain/MINDS project aims to further understand the human brain and neuropsychiatric disorders through ‘‘translatable’’ biomarkers. Here, we describe the neuroethical issues of the project that have arisen from clinical data collection and the use of biological models of neuropsychiatric disorders.
Mismatch negativity (MMN) reduction is one of the most robust findings in schizophrenia that is related with early psychosis, functional abilities and translatable into animal models. We reviewed clinical MMN research and basic research in animal models and human intracranial recording for understanding neural mechanism of MMN.
We demonstrated that the gamma-band auditory steady-state response (ASSR), which is significantly impaired in patients with schizophrenia compared with healthy controls, is significantly correlated with plasma levels of D-serine, a co-agonist of the glycine binding site of N-methyl-D-aspartate (NMDA) receptor, in the schizophrenia group. These findings suggest that the gamma-band ASSR may reflect NMDA receptor function in schizophrenia.
We developed a high-throughput neurohistological and computational pipeline to accurately map individual brains into a common reference atlas. This method uses a grid-based tracer injection strategy for systematic mesoscale connectivity mapping, providing the first detailed and large-scale presentation of a full resolution microscopic online database (http://marmoset.brainarchitecture.org/). Our method will lay a foundation for subsequent scientific outputs and help others establish their own workflows in the future.
We compare the performance of recently developed genetically encoded voltage indicators (GEVIs) under multiple experimental conditions in vitro and in vivo. Each indicator has advantages and disadvantages, and no single GEVI is ideal for every experiment. The results provide a guide for choosing optimal GEVIs for specific applications.
Recording the activity of neurons over large brain regions requires expanding the field of view of the optics without losing on spatial and temporal resolution. Here, this team reports a micro-opto-mechanical device that enables two-photon imaging across distant cortical areas around 6 mm apart in the mouse.
It remains unclear how direct and indirect pathways of the basal ganglia signal functional information for a goal-directed adaptive behavior. Combining electrophysiology and optogenetics in behaving rats, we found the direct pathway neurons reselect the same action after reward outcome, whereas indirect pathway neurons switch to the other action after no-reward outcome.
The research team led by Hideyuki Okano and Junichi Ushiba (Keio University) demonstrate calcium imaging from neuronal populations using a miniature fluorescence microscope in naturally behaving non-human primates (NHPs), common marmosets. This technique marks an advance beyond methods using fixed head positioning, which limits the study of complex, self-determined behaviors such as social interactions or fear/anxiety.
MARCKS Phosphorylation at Ser46 reflects neurite degeneration and is a candidate marker for presymptomatic and preaggretaion pathology of Alzheimer’s disease. Here, we demonstrate the similar change in Parkinson’s disease and Dementia with Lewy body prior to alpha-synuclein aggregation, and suggest an ultra-early stage pathology shared by different groups of neurodegenerative diseases.
The ventral tegmental area (VTA) and substantia nigra (SN) are involved in dopaminergic brain functions. Given that there are no VTA or SN anatomical MRI templates for Asian people, we created these templates and showed suitability for Asian brains using anatomical and resting state functional MRI data.
The research team led by Profs. Norio Ozaki (Nagoya University) and Hideyuki Okano (Keio University) revealed that a rare RELN variant, initially identified in a schizophrenic patient, causes a loss of directional stability during neuronal migration using human iPSCs generated from the patient. These findings are expected to contribute to understanding the molecular pathophysiology and/or developing drugs for mental disorders.
Arioka Y, Shishido E, Kubo H, Kushima I, Yoshimi A, Kimura H, Ishizuka K, Aleksic B, Maeda T, Ishikawa M, Kuzumaki N, Okano H, Mori D, Ozaki N: Single-cell trajectory analysis of human homogenous neurons carrying a rare RELN variant. Transl Psychiatry 8 (1):129, 2018
The 41st Annual Meeting of the Japan Neurosciene Society – International Symposium on Global Neuroscience Cooperation sponsored by Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS)
The 41st Annual Meeting of the Japan Neurosciene Society - International Symposium on Global Neuroscience Cooperation will take place on the following schedule.
Date: Sunday, July 29th , 2018
Location: Kobe Convention Center Kobe International Conference Center 3F Venue 7(504+505)
Norihiro Sadato (Department of System Neuroscience, National Institute for Physiological Sciences)
Kiyoto Kasai (Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo)
Hideyuki Okano (Department of Physiology, Keio University School of Medicine)
Takuya Hayashi (Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies)
Intellectual deterioration may play a key role in work disturbances in patients with schizophrenia. The study demonstrated probabilistic models to estimate work status in patients with schizophrenia based on relevant factors including intellectual deterioration. Feedback on work status would support social rehabilitation in patients with schizophrenia.
The present study demonstrated that tau pathology in orbitofrontal cortex (OFC) may provoke focal neurotoxicity in OFC and the following disruption of the OFC-uncinate fasciculus network, leading to the emergence and progression of apathy in Alzheimer’s disease. The current data also raise the possibility that emerging antitau drugs would be efficacious for suppressing apathy.
By combining an 8K ultra-high-definition camera with spinning-disk one-photon confocal microscopy, we succeeded in imaging of activity of presynaptic axonal boutons of neurons projecting to the motor cortex in a behaving mouse. We detected axonal boutons with highly correlated activity over the 1 mm2 field.
ORIGINAL ARTICLE Abe, H. et al.
CRMP2‑binding compound, edonerpic maleate, accelerates motor function recovery from brain damage. Science 360, 50–57 (2018)
This article was published in "Biochemical and Biophysical Research Communications, Volume 500, Issue 2".
Brain damage such as stroke is a devastating neurological condition, which may severely compromise patient quality of life. No effective medication-mediated intervention to accelerate rehabilitation has been established. We found that a small compound, edonerpic-maleate, facilitated experience-driven synaptic glutamate AMPAreceptor delivery and resulted in the acceleration of motor function recovery after brain damage in a training-dependent manner.
Bioluminescence is a natural light source based on luciferase catalysis of its substrate luciferin. We performed directed evolution on firefly luciferase using a red-shifted and highly deliverable luciferin analog to establish AkaBLI, an all-engineered bioluminescence in vivo imaging system.
This research result was published in "Science 23 Feb 2018".
Mutations in the progranulin (PGRN) gene cause a tau pathology-negative and TDP43 pathology-positive form of frontotemporal lobar degeneration (FTLD-TDP). We generated a knock-in mouse harboring the R504X mutation (PGRN-KI).
This research result was published on Nature Communications, 30 January 2018.
Subcortical regions have a pivotal role in cognitive, affective, and social functions in humans, and the structural and functional abnormalities of the regions have been associated with various psychiatric disorders.
This research result was published on Scientific Reports, volume 8, 19 January 2018.
We examined the neural basis of persuasion-induced changes in attitude toward and away from norms using fMRI. We measured brain activity while human participants were exposed to persuasive messages directed toward specific norms.
This research result was published on Scientific Reports volume 7, Article number: 16295, 24 November 2017.
Brain/MINDS Data Portal has been launched
“Neurobiology: learning from marmosets” in nature methods
Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) was introduced on Nature Methods
Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) was introduced by Newton
“Worldwide initiatives to advance brain research” in Nature Neuroscience
Brain/MINDS updated brochure
Researchers at the RIKEN Brain Science Institute and collaborative project have discovered that the benefits of stimulating the brain with direct current come from its effects on astrocytes — not neurons — in the mouse brain. Published in Nature Communications, the work shows that applying direct current to the head releases synchronized waves of calcium from astrocytes that can reduce depressive symptoms and lead to a general increase in neural plasticity — the ability of neuronal connections to change when we try to learn or form memories.
In cerebellar Purkinje cells (PCs), dendritic territories by climbing and parallel fiber (PF) innervations are segregated. Here, we show that the segregation of territories occurs as a result of elimination of PF synapses from the proximal dendrites, and that PF synapse elimination is controlled by the type 1 metabotropic glutamate receptor to protein kinase Cg signaling pathway in PCs.
Press Release Mirror Neurons in a New World Monkey, Common Marmoset
The research team including researchers from NCNP and RIKEN BSI found neurons in the ventrolateral frontal cortex with characteristic “mirror” properties quite similar to those in macaques. This finding suggests that mirror neurons occur in a common ancestor of New and Old World monkeys and its common properties are preserved during the course of primate evolution.
Researchers at the RIKEN Brain Science Institute in Japan have developed a new system for imaging the activity of individual neurons in the marmoset brain. Published in Cell Reports, the study shows how amplifying genetically encoded fluorescent signals with TET-inducible gene expression allows hundreds of individual neurons in the primate brain to be imaged simultaneously over a period of several months.
It remains unclear how readiness for Ca2+ -dependent exocytosis depends on varying degrees of SNARE complex assembly. We demonstrated the SNARE assembly using ﬂuorescence lifetime imaging (FLIM) of Forster resonance energy transfer (FRET) between three pairs of neuronal SNAREs in presynaptic boutons and pancreatic beta cells in the islets of Langerhans.
The research team including researchers from RIKEN BSI and NIPS established a new method to visualize dendritic spines in the living marmoset brain. The method that utilizes two-photon microscopy in combination with virus vectors to enhance the expression of fluorescent signals makes it possible to study neural circuits in primate brains.
Press Release Real x-ray vision: see-through brains ready for study
Researchers at the RIKEN Brain Science Institute in Japan have developed a new technique for creating transparent tissue that can be used to illuminate 3D brain anatomy at very high resolutions. Published in Nature Neuroscience, the work showcases the new technology and its practical importance in clinical science by showing how it has given new insights into Alzheimer’s disease plaques.
Brain/MINDS Symposium in Neuroscience 2015 has been concluded successfully
Brain/MINDS Symposium in Neuroscience 2015
The research team led by Prof. Okazawa (Tokyo Medical and Dental University) developed a new technique for observation
of autophagy in the brain in vivo, and revealed unexpected roles of autophagy in Alzheimer's disease
including the increase of intracellular Amyloid beta by starvation and circadian rhythm of neuronal autophagy activity.
Dr. H. Okano published the papaer “Brains, Genes, and Primates” in Neuron
Brains, Genes, and Primates
The special issue “Marmoset Neuroscience” has been published as the April issue of Neuroscience Research
Brain/MINDS: brain-mapping project in Japan- Philosophical Transactions B
Hideyuki Okano, Atsushi Miyawaki, Kiyoto Kasai
Brain/MINDS was relegated to Japan Agency for Medical Research and Development From April, 2015
Welcome! Our website is now open to the world.
Brain-mapping projects using the common marmoset
Hideyuki Okano, Partha Mitra