Optogenetic activation of the ventral tegmental area-hippocampal pathway facilitates rapid adaptation to changes in spatial goals.

Animal adaptation to environmental goals to pursue rewards is modulated by dopamine. However, the role of dopamine in the hippocampus, involved in spatial navigation, remains unclear. Here, we studied dopaminergic inputs from the ventral tegmental area (VTA) to the hippocampus, focusing on spatial goal persistence and adaptation.

Utilizing a Reconfigurable Maze System to Enhance the Reproducibility of Spatial Navigation Tests in Rodents.

Several maze shapes are used to test spatial navigation performance and behavioral phenotypes. Traditionally, each experiment requires a unique maze shape, thus requiring several separate mazes in different configurations. The maze geometry cannot be reconfigured in a single environment to accommodate scalability and reproducibility.

Association between the superior longitudinal fasciculus and perceptual organization and working memory: A diffusion tensor imaging study.

The superior longitudinal fasciculus (SLF) is a white matter structure that has long bidirectional projections among the prefrontal, temporal, occipital, and parietal cortices and extends over a wide area in a human brain. Recently, anatomical details of the SLF have been clarified using a diffusion tensor imaging (DTI) template of subjects from the Human Connectome Project. However, the neurobehavioral functions of the SLF have not been fully elucidated.

Ethnicity-Dependent Effects of Schizophrenia Risk Variants of the OLIG2 Gene on OLIG2 Transcription and White Matter Integrity.

Previous studies have indicated associations between several OLIG2 gene single-nucleotide polymorphisms (SNPs) and susceptibility to schizophrenia among Caucasians. Consistent with these findings, postmortem brain and diffusion tensor imaging studies have indicated that the schizophrenia-risk-associated allele (A) in the OLIG2 SNP rs1059004 predicts lower OLIG2 gene expression in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia patients and reduced white matter (WM) integrity of the corona radiata in normal brains among Caucasians. In an effort to replicate the association between this variant and WM integrity among healthy Japanese, we found that the number of A alleles was positively correlated with WM integrity in some fiber tracts, including the right posterior limb of the internal capsule, and with mean blood flow in a widespread area, including the inferior frontal operculum, orbital area, and triangular gyrus.

Plasma levels of matrix metalloproteinase-9 (MMP-9) are associated with cognitive performance in patients with schizophrenia.

Aim: Matrix metalloproteinase-9 (MMP-9) has been shown to modulate synaptic plasticity and may contribute to the pathophysiology of schizophrenia. This study investigated the peripheral levels of MMP-9 and its association with cognitive functions in patients with schizophrenia to see the possible involvement of MMP-9 in pathophysiology of schizophrenia, especially in cognitive decline.

Methods: We measured the plasma levels of MMP-9 in 257 healthy controls and 249 patients with schizophrenia, including antipsychotic drug-free patients.

The Reconfigurable Maze Provides Flexible, Scalable, Reproducible, and Repeatable Tests.

Multiple mazes are routinely used to test the performance of animals because each has disadvantages inherent to its shape. However, the maze shape cannot be flexibly and rapidly reproduced in a repeatable and scalable way in a single environment. Here, to overcome the lack of flexibility, scalability, reproducibility, and repeatability, we develop a reconfigurable maze system that consists of interlocking runways and an array of accompanying parts.

Brain morphological and functional features in cognitive subgroups of schizophrenia.

Aim: Previous studies have reported different brain morphologies in different cognitive subgroups of patients with schizophrenia. We aimed to examine the brain structures and functional connectivity in these cognitive subgroups of schizophrenia.

Methods: We compared brain structures among healthy controls and cognitively deteriorated and preserved subgroups of patients with schizophrenia according to the decline in IQ.

White matter microstructural alterations across four major psychiatric disorders: mega-analysis study in 2937 individuals.

Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites).

A new inbred strain of Fawn-Hooded rats demonstrates mania-like behavioural and monoaminergic abnormalities.

The Fawn-Hooded (FH) rat carries a gene mutation that results in a dysfunctional serotoninergic system. However, previous studies have reported differing features between the FH/Wjd and FH/Har strains. We aimed to compare the behavioural and neurobiological features of FH/HamSlc rats with those of Fischer 344 rats.

Differentiation of schizophrenia using structural MRI with consideration of scanner differences: A real-world multisite study.

Aim: Neuroimaging studies have revealed that patients with schizophrenia exhibit reduced gray matter volume in various regions. With these findings, various studies have indicated that structural MRI can be useful for the diagnosis of schizophrenia. However, multisite studies are limited.

Eye movement abnormalities and their association with cognitive impairments in schizophrenia.

Background: Eye movement abnormalities have been identified in schizophrenia; however, their relevance to cognition is still unknown. In this study, we explored the general relationship between eye movements and cognitive function.

Methods: The three eye movement measures (scanpath length, horizontal position gain, and duration of fixations) that were previously reported to be useful in distinguishing subjects with schizophrenia from healthy subjects, as well as Wechsler Adult Intelligence Scale-III (WAIS-III) scores, were collected and tested for association in 113 subjects with schizophrenia and 404 healthy subjects.

Predicting work outcome in patients with schizophrenia: Influence of IQ decline.

Background: Patients with schizophrenia show various trajectories in intelligence. However, whether the degree of IQ decline is associated with functional outcomes remains unclear. The purposes of the study were 1) to determine whether IQ decline was related with work outcome, and 2) to perform predictions for attaining a certain amount of work measured by work hours.

Role of frontal white matter and corpus callosum on social function in schizophrenia.

Patients with schizophrenia show severe impairment in social function and have difficulty in their daily social life. Although a recent large-scale multicenter study revealed alterations in white matter microstructures, the association between these anatomical changes and social dysfunction in schizophrenia remains unknown. Therefore, we investigated the association between the white matter integrity of regions of interest and social function in schizophrenia.

Plasma Levels of Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2) Are Associated with Hippocampal Volume and Cognitive Performance in Patients with Schizophrenia.

Background: An imbalance in the inflammatory tumor necrosis factor system, including soluble tumor necrosis factor receptor 2 (sTNFR2), may contribute to the pathophysiology of schizophrenia.

Methods: We measured the plasma levels of sTNFR2 in 256 healthy controls and 250 patients with schizophrenia including antipsychotic drug-free patients and treatment-resistant patients. We also explored the possible association between plasma sTNFR2 levels and cognitive performance in healthy controls and patients with schizophrenia using the Wechsler Adult Intelligence Scale, Third Edition, the Wechsler Memory Scale-Revised, and the Rey Auditory Verbal Learning Test.

TARP γ-2 and γ-8 Differentially Control AMPAR Density Across Schaffer Collateral/Commissural Synapses in the Hippocampal CA1 Area.

Unlabelled: The number of AMPA-type glutamate receptors (AMPARs) at synapses is the major determinant of synaptic strength and varies from synapse to synapse. To clarify the underlying molecular mechanisms, the density of AMPARs, PSD-95, and transmembrane AMPAR regulatory proteins (TARPs) were compared at Schaffer collateral/commissural (SCC) synapses in the adult mouse hippocampal CA1 by quantitative immunogold electron microscopy using serial sections. We examined four types of SCC synapses: perforated and nonperforated synapses on pyramidal cells and axodendritic synapses on parvalbumin-positive (PV synapse) and pravalbumin-negative interneurons (non-PV synapse).

Essential role of excessive tryptophan and its neurometabolites in fatigue.

Purpose: Serotonin, a neurotransmitter synthesized from tryptophan, has been proposed to play a key role in central fatigue. In this study, we examined whether tryptophan itself and/or its two metabolites, kyneurenic acid (KYNA) and quinolinic acid (QUIN), are involved in central fatigue.

Materials And Methods: Experiments were conducted using Sprague-Dawley rats (SDR) and Nagase analbuminemic rats (NAR).

Glutamate receptor δ2 is essential for input pathway-dependent regulation of synaptic AMPAR contents in cerebellar Purkinje cells.

The number of synaptic AMPA receptors (AMPARs) is the major determinant of synaptic strength and is differently regulated in input pathway-dependent and target cell type-dependent manners. In cerebellar Purkinje cells (PCs), the density of synaptic AMPARs is approximately five times lower at parallel fiber (PF) synapses than at climbing fiber (CF) synapses. However, molecular mechanisms underlying this biased synaptic distribution remain unclear.