Biology subjects

Kojima, K.

Publications and source records attributed to Kojima, K..

At least 19 recordsLinked to original sources

bioRxiv2026

A bistable UV-sensitive opsin from a reef building coral showing a switchable and tunable regulation of Gs-signaling by different wavelengths of light

Cnidarians possess large number of opsins in their genomes for their various photoreceptive functions. In particular, they uniquely possess Gs-coupled opsins that induce intracellular cAMP accumulation in a light-dependent manner. These Gs-coupled opsins, cnidopsins, are powerful optogenetic tools manipulating cAMP-dependent cellular responses. In this study, we characterized a cnidopsin, named as AtCnidop3a, from the coral Acropora tenuis as a Gs-coupled and UV-sensitive bistable pigment. This cnidopsin showed a large spectral shift upon activation from absorption maxima from 395 nm to 560 nm, and the resting and activated states are interconvertible by illumination with UV (or violet) and orange light. The activated state efficiently activated Gs proteins and elevated intracellular cAMP levels in mammalian cultured cells. To engineer the opsin mutant that can be turned on and off upon long wavelength light illumination by utilizing the large spectral separation, negatively charged amino acids were introduced near the retinal Schiff base region. Among tested opsin mutants, the Y1133.28E mutant is capable of being activated by green light unlike the wild-type while retaining the property of being inactivated by orange light like the wild-type, indicating successful conversion of the opsin to a visible light sensitive bistable pigment. The visible light-induced cAMP regulation of the Y1133.28E mutant was enhanced by an additional L942.61G substitution. Our characterization and engineering of the cnidopsin revealed functional diversity of cnidarian opsins and its potential utility as optogenetic tools regulating Gs-dependent physiological responses.

biochemistry↗

bioRxiv2026

Hyaluronic Acid Plays Differential Molecular Weight and Concentration Dependent Pathway Centric Changes to Human Lung Derived Microvascular Endothelial Cells in Culture

BackgroundHyaluronan (HA) is a major extracellular matrix glycosaminoglycan that regulates vascular integrity and immune signaling in the lung. Its biological effects are strongly size-dependent, with high-molecular-weight HA (HMW-HA) generally protective and low-molecular-weight HA (LMW-HA) pro-inflammatory. However, how different HA sizes and concentrations globally remodel endothelial cell signaling remains poorly understood. MethodsHuman lung microvascular endothelial cells (HULEC-5a) were treated with physiologic (200 ng/mL) or supraphysiologic (1 {micro}g/mL) concentrations of LMW-, medium-molecular-weight (MMW-), or HMW-HA. Cell viability was confirmed by LDH assay. Quantitative proteomics with downstream Ingenuity Pathway Analysis (IPA) was used to profile HA-induced signaling networks. ResultsProteomic analysis revealed a conserved HA-response signature across all conditions involving cell cycle regulation, senescence, and immune modulation, with distinct size-and dose-dependent differences. At supraphysiologic concentrations, HMW-HA suppressed proliferative and inflammatory pathways, consistent with a protective, quiescent phenotype. LMW-HA induced the broadest stress-associated proteomic changes, consistent with its role as a damage-associated molecular pattern. Unexpectedly, physiologic MMW-HA elicited the strongest responses, driving metabolic and cytoskeletal pathways including insulin signaling and Rho GTPase activity. Network analysis highlighted 176 overlapping pathways across HA treatments, with unique contributions of LMW- and HMW-HA to stress- versus barrier-stabilizing signaling, respectively. ConclusionHA is not a passive structural molecule but an active regulator of endothelial signaling, with effects shaped by both molecular weight and concentration. Our findings identify a distinct role for MMW-HA at physiologic levels and highlight how HA fragmentation and accumulation may contribute to endothelial dysfunction in lung injury, with implications for targeted HA-based therapies.

cell biology↗

bioRxiv2026

Rapid neural analysis of linguistic stress and meter in continuous speech

Continuous speech evolves around vowels, the centerpieces of individual syllables. Vowels vary in linguistic and acoustic salience: Linguistically, stressed syllables are more salient than unstressed syllables: Stress patterns convey critical lexico-semantic and prosodic information, and their regularity defines the speech meter. Acoustically, English vowel intensity cues lexical stress but also marks salient syllables irrespective of stress status. Recent evidence demonstrates rapid neural analysis of vowel intensity and identity during perception of continuous speech. Here, we probe how these processes integrate lexical stress and metrical regularity. We recorded EEG while participants (n=26) listened to childrens stories with either an irregular, speech-like meter, or a regular poetic meter. Stress and meter modulated cortical encoding of vowels throughout processing: Preparatory activity preceded vowel onsets in an irregular meter only, and early sensory responses were enhanced for unstressed vowels, suggesting additional resource allocation during processing of uncertain and less discriminable speech sounds. In contrast, later processing (300-500ms) was stronger for stressed syllables and in irregular meters, suggesting a combined effect of uncertainty and informational content. Finally, responses were stronger for small intensity rises within metrically predicted stressed vowels than in all other conditions. In the time-frequency domain, the spectral profile of neural phase-locking corresponded to spectral signatures of individual evoked responses, syllable and stress rates in the stimuli. Overall, our findings reveal rapid neural integration of stress and metrical expectations in neural processing of continuous speech. These dynamics may underlie the perceptual benefits of metrically regular speech, such as poetry and song lyrics.

neuroscience↗

bioRxiv2025

Structure-function analysis of lithium-ion selectivity of voltage-gated sodium channel

Voltage-gated sodium channels (Navs) selectively conduct Na+ to generate action potentials. Na+ permeates Navs with significantly higher efficiency than many other cations, but Li+ can also permeate Navs to a comparable extent as Na+. It had been known that Li+ in blood enters cell via Navs and effects beneficially on various neuropathies. However, the molecular basis of the high Li+ selectivity of Navs had been unclear. In this study, using a prokaryotic Nav, we successfully created the first Nav mutant that is more selective for Li+ than for Na+. Electrophysiological and crystallographic analyses revealed the critical determinants of high Li+ selectivity: the strong electrostatic interaction between the ion pathway and hydrated ions, and the smaller number of hydration water exchanges within the ion pathway. Additionally, the extensive interactions around the ion pathway were shown to support monovalent cation selectivity. New drug directions based on the molecular basis for Li+ permeation may target various neurological disorders and clarify the broader biological effects of lithium.

biophysics↗

bioRxiv2025

Housing environment bilaterally alters transcriptomic profile in the rat hippocampal CA1 region

Brain asymmetry is a fundamental feature of neural organization. However, the molecular basis of hippocampal lateralization in response to environmental stimuli remains poorly understood. Here, we examined the transcriptomic profiles of the left and right hippocampal CA1 regions in rats reared under isolated or enriched housing conditions to elucidate hemisphere-specific responses and shared molecular adaptations. RNA-sequencing analysis revealed lateralized differences in the number and identity of differentially expressed genes, accompanied by distinct biological themes, as indicated by overrepresentation and gene set enrichment analysis. The left CA1 region was prominently engaged in pathways related to synaptic organization and mitochondrial function, whereas the right CA1 region exhibited enrichment in transcriptional regulation and RNA metabolic processes. Despite these asymmetries, co-expression and protein-protein interaction network analyses revealed shared molecular architectures. Immediate early genes formed consistent central hubs across both hemispheres, and a common Mecp2-Grin2b-Cdkl5-Tet3 protein interaction cluster was identified as a potential integrative regulatory module. Additional enrichment analysis of differentially expressed genes shared between hemispheres further highlighted conserved responses, particularly in synaptic plasticity and cell-cell communication. Together, these findings demonstrate that the left and right CA1 regions employ distinct yet partially convergent transcriptional programs to adapt to environmental stimuli. This coordinated molecular asymmetry provides novel insights into hippocampal lateralization and its role in experience-dependent brain plasticity.

neuroscience↗

bioRxiv2025

LRP2 is a potential molecular target for pathological myopia

High myopia (HM) and posterior staphyloma (PS) are major causes of vision loss worldwide. Genetic and environmental factors, especially light exposure, contribute to myopia. Mutations in low-density lipoprotein-related receptor type 2, LRP2 cause syndromic myopia, and the Foxg1-Cre-Lrp2lox/lox mouse is a model for myopia and PS but the involvement of LRP2 in non-syndromic HM (NSHM) was unknown. We showed that LRP2 levels were decreased in the vitreous of 25 patients with NSHM and PS, and that in human donor eyes affected by PS, LRP2 expression was reduced in the neural retina and retinal pigment epithelium (RPE). The morphologic changes of these RPE were similar to those observed in the RPE of the Foxg1- Cre-Lrp2lox/lox mouse. In iPSc-derived human RPE cells (iRPE), LRP2 was expressed at a functional location, and LRP2 silencing by a specific siRNA regulated genes belonging to pathways involved in eye and neuronal development, visual perception, tissue remodeling, hormone metabolism and RPE structure, demonstrating that LRP2 orchestrates in RPE, functions that are essential for eye growth. Exposure of iRPE to light with LEDs of different wavelengths upregulated LRP2 expression, with higher efficacy for red light. Conversely, LRP2 expression was downregulated after cortisol exposure. Our findings link LRP2 to myopization and environmental factors and highlight its role in NSHM and PS in humans. LRP2 appears to be a viable target for interventional strategies in the treatment of NSHM. One Sentence SummaryLRP2, pivotal in the regulation of eye growth, exhibits a decrease in high myopic eyes. Its expression is augmented by light exposure in retinal pigment epithelial cells.

pathology↗

bioRxiv2024

Effects of tenascin-C on dental pulp tissue in mice in vivo and on the proliferation and differentiation of dental pulp stem cells into odontoblasts and calcification in vitro

This study aimed to investigate the effects of tenascin-C (TN-C) on dental pulp tissue and on dental pulp stem cells (DPSCs). In in vivo studies, A collagen sponge with phosphate-buffered saline (PBS) for the control group or with TN-C for the experimental group was placed over the dental pulp of mice. The root pulp was excised at 7 and 21 days postoperatively and was observed microscopically using HE staining and immunohistochemistry. Inflammatory cells were found in the entire pulp tissue in the control group but no inflammatory cells were identified in the pulp tissue in the TN-C-treated experimental group. Further, nestin-positive cells at 7 days and dentin sialophosphoprotein (DSPP)-positive cells at 21 days were seen in the experimental group. In in vitro studies, DPSCs were cultured in a medium with or without TN-C, after which the proliferation rate of DPSCs was measured mRNA expression levels were examined using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the formation of calcified nodules was investigated using alizarin red staining. The cell proliferation rate was not significantly different between the experimental and control groups. The expression of nestin mRNA on day 7 was significantly higher in the experimental group than in the control group (P<0.05), but the expression of osteocalcin (OCN) mRNA was significantly higher in the control group than in the experimental group (P<0.05). More calcified nodules formed in the control group than in the experimental group. These results suggest that TN-C regulates inflammation during the healing process in the dental pulp and induces the differentiation of dental pulp into odontoblast-like cells. Further, TN-C promotes the early differentiation of DPSCs into odontoblast-like cells, which suggests that TN-C may further contribute to the inhibition of excessive dentin formation.

cell biology↗

bioRxiv2023

Can Colpoda travel across oceans? Salinity tolerance of resting cysts may enable global dispersal of the species.

Protist species are distributed worldwide. The processes that enabled this global distribution are unclear. One possible means is through the oceanic dispersal of freshwater protists, although this has not been investigated in detail to date. Here, the ability of resting cysts to tolerate saline conditions is examined as a possible mechanism that enables the oceanic dispersal of protists. Resting cysts of Colpoda cucullus, a freshwater soil protist, can tolerate saline conditions of at least 3.5% NaCl for more than one week. A transcriptome analysis showed that the relative levels of expression of genes associated with membrane function are increased in resting cysts, indicating that salinity tolerance is associated with reconstruction of the cell membrane. Additionally, the outer layer of the cyst wall, a shell-like ectocyst, includes chitin. This may function as a form of "biological armor" that protects the cell from physical stress during oceanic dispersal. Teaser: Fresh water protists may be dispersed across oceans by formation of resting cysts that can tolerate saline conditions.

zoology↗

bioRxiv2023

Essential role of an acidic endosomal environment in JAK3-mediated signal transduction

The endosome, an acidic organelle, is a platform for endocytic trafficking and signal transduction. Chloroquine, an intercellular acidic vesicle neutralizer (IAVN), has been used to treat autoimmune diseases. Its immunosuppressive mechanism remains unclear, although several modes of action attributable to lysosomal dysfunction have been postulated. This study found that IAVNs, including chloroquine, can selectively interfere with common cytokine receptor {gamma} chain ({gamma}c) cytokine-induced signal transduction. Our data show that JAK3 targets endosomal membranes in an acidic pH-dependent manner, which is essential for {gamma}c-cytokine-induced functional signal complex formation and signal activation. Among IAVNs, Monensin and similar ionophores were particularly effective in suppressing {gamma}c-cytokine-induced cell proliferation in vitro. Monensin exerted therapeutic effects in a collagen-induced arthritis mouse model by interfering with T helper 17 cells. Our findings help further understand the immunosuppressive mechanism of IAVNs and unveil the spatial regulation of JAK3-mediated signal transduction via endosomes.

immunology↗

bioRxiv2023

Hemopexin Reverses Activation of Lung eIF2a and Decreases Mitochondrial Injury in Chlorine Exposed Mice

We assessed the mechanisms by which non-encapsulated heme, released in the plasma of mice post exposure to chlorine (Cl2) gas, resulted in the initiation and propagation of acute lung injury. We exposed adult C57BL/6 male and female to Cl2 (500 ppm for 30 min) in environmental chambers and returned them to room air and injected them intramuscularly with a single dose of human hemopexin (hHPX; 5 {micro}g/ g BW), the most efficient scavenger of heme, 30-60 min post exposure. Concentrations of hHPX in plasma of air and Cl2 exposed mice were 9081{+/-}900 vs. 1879{+/-} 293 at 6 h and 2966{+/-}463 vs. 1555{+/-}250 at 50 h post injection (ng/ml; X{+/-}1 SEM=3; p<0.01). Cl2 exposed mice developed progressive acute lung injury post exposure characterized by increased concentrations of plasma heme, marked inflammatory response, respiratory acidosis and increased concentrations of plasma proteins in the alveolar space. Injection of hHPX decreased the onset of acute lung injury at 24 h post exposure; mean survival, for the saline and hHPX groups were 40 vs. 80% (P<0.001) at 15 d post exposure. Non-supervised global proteomics analysis of mouse lungs at 24 h post exposure, revealed the upregulation of 92 and downregulation of 145 lung proteins. Injection of hHPX at one h post exposure moderated the Cl2 induced changes in eighty-three of these 237 lung proteins. System biology analysis of the global proteomics data showed that hHPX reversed changes in mitochondrial dysfunction and elF2 and integrin signaling. Western blot analysis of lung tissue showed significant increase of phosphorylated elF2 at 24 h post exposure in vehicle treated mice but normal levels in those injected with hHPX. Similarly, RT-PCR analysis of lung tissue showed that hHPX reversed the onset of mtDNA lesions. A form of recombinant human hemopexin generated in tobacco plants was equally effective in reversing acute lung and mtDNA injury. The results of this study offer new insights as to the mechanisms by which exposure to Cl2 results in acute lung injury and to the therapeutic effects of hemopexin.

physiology↗

bioRxiv2023

DNA methylation signature in NSD2 loss-of-function variants appeared similar to that in Wolf-Hirschhorn syndrome

PurposeWolf-Hirschhorn syndrome (WHS), a contiguous gene syndrome caused by the hemizygous deletion of the distal short arm of chromosome 4 where NSD2 is, reportedly exhibits specific DNA methylation signatures in peripheral blood cells. However, responsible genomic loci for signatures are unreported. The objective of the study is to define the loci of WHS-related DNA methylation signatures and to explore the role of NSD2 for the signatures. MethodsWe conducted genome-wide methylation analysis of individuals with WHS or NSD2 variants using array. We studied genome-edited knock in mice or induced pluripotent stem cells to explore the function of NSD2 variants which are observed in congenital anomaly cases. ResultsThree undiagnosed cases with NSD2 variants showed WHS-related DNA methylation signatures. These variants were validated to be NSD2 loss-of-function in induced pluripotent stem cells or genome-edited knock-in mice. p.Pro905Leu variant decreased Nsd2 protein levels, and changed Histone H3-Lysine 36 demethylation levels in similar way in the same genomic regions as Nsd2 knock out mice regulated. Nsd2 knock out mice exhibited common DNA methylation changes. ConclusionThese results revealed that WHS-related DNA methylation signatures are dependent on NSD2 dysfunction and are useful in diagnosing NSD2 variants of unknown significance.

genetics↗

bioRxiv2022

mRNA-based generation of marmoset PGCLCs capable of differentiation into gonocyte-like cells

Primate germ cell development remains largely unexplored due to limitations in sample collection and the long duration of development. In mice, primordial germ cell-like cells (PGCLCs) derived from pluripotent stem cells (PSCs) can develop into functional gametes by in vitro culture or in vivo transplantation. Such PGCLC-mediated induction of mature gametes in primates is highly useful for understanding human germ cell development. Since marmosets generate functional sperm earlier than other species, recapitulating the whole male germ cell development process is technically more feasible. Here, we induced the differentiation of iPSCs into gonocyte-like cells via PGCLCs in marmosets. First, we developed an mRNA transfection-based method to efficiently generate PGCLC. Subsequently, to promote PGCLC differentiation, xenoreconstituted testes (xrtestes) were generated in the mouse kidney capsule. PGCLCs show progressive DNA demethylation and stepwise expression of developmental marker genes. This study provides an efficient platform for the study of marmoset germ cell development. HighlightsO_LIAn mRNA transfection-based PGCLC induction method is developed C_LIO_LIMarmoset PGCLCs are efficiently induced from iPSCs C_LIO_LIMarmoset PGCLCs differentiate into gonocyte-like cells in mouse kidneys C_LIO_LIDevelopmentally regulated expression and demethylation are recapitulated C_LI eTOC blurbWatanabe et al. efficiently induced marmoset primordial germ cell-like cells (PGCLCs) using an mRNA transfection-based approach. PGCLCs further develop into gonocyte-like cells in the xenoreconstituted testes constructed under mouse kidney capsules. This system faithfully reproduced in vivo developmental processes (e.g., stage-specific expression of developmentally regulated genes and DNA demethylation).

developmental biology↗

bioRxiv2022

The SARS-CoV-2 Spike S1 Protein Induces Global Proteomic Changes in ATII-Like Rat L2 Cells that are Attenuated by Hyaluronan

The COVID-19 pandemic continues to impose a major impact on global health and economy since its identification in early 2020, causing significant morbidity and mortality worldwide. Caused by the SARS-CoV-2 virus, along with a growing number of variants that have been characterized to date, COVID-19 has led to 571,198,904 confirmed cases, and 6,387,863 deaths worldwide (as of July 15th, 2022). Despite tremendous advances in our understanding of COVID19 pathogenesis, the precise mechanism by which SARS-CoV2 causes epithelial injury is incompletely understood. In this current study, robust application of global-discovery proteomics applications combined with systems biology analysis identified highly significant induced changes by the Spike S1 protein of SARS-CoV-2 in an ATII-like Rat L2 cells that include three significant network hubs: E2F1, CREB1/ RelA, and ROCK2/ RhoA. Separately, we found that pre-treatment with High Molecular Weight Hyaluronan (HMW-HA), greatly attenuated the S1 effects. Immuno-targeted studies carried out on E2F1 and Rock2/ RhoA induction and kinase-mediated activation, in addition to cell cycle measurements, validated these observations. Taken as a whole, our discovery proteomics and systems analysis workflow, combined with standard immuno-targeted and cell cycle measurements revealed profound and novel biological changes that contribute to our current understanding of both Spike S1 and Hyaluronan biology. This data shows that the Spike S1 protein may contribute to epithelial injury induced by SARS-CoV-2. In addition, our work supports the potential benefit of HMW-HA in ameliorating SARS CoV2 induced cell injury.

systems biology↗

bioRxiv2022

Proton-pumping rhodopsins in marine diatoms

Diatoms are a major phytoplankton group responsible for about 20% of Earths primary production. They carry out photosynthesis inside the plastid, an organelle obtained through eukaryote-eukaryote endosymbiosis. Recently, microbial rhodopsin, a photoreceptor distinct from chlorophyll-based photosystems, has been identified in certain diatoms. However, the physiological function of diatom rhodopsin is not well understood. Here we show that the diatom rhodopsin acts as a light-driven proton pump and localizes to the outermost membrane of the four membrane-bound complex plastids. Heterologous expression techniques were used to investigate the protein function and subcellular localization of diatom rhodopsin. Using model simulations, we further evaluated the physiological role of the acidic pool in the plastid produced by proton-transporting rhodopsin. Our results propose that the rhodopsin-derived acidic pool may be involved in a photosynthetic CO2-concentrating mechanism and assist CO2 fixation in diatom cells.

microbiology↗

bioRxiv2021

Structure and mechanism of oxalate transporter OxlT in an oxalate-degrading bacterium in the gut microbiota

Oxalobacter formigenes is an oxalate-degrading bacterium in the gut microbiota that absorbs food-derived oxalate to use this as a carbon and energy source and thereby helps reduce the risk of kidney stone formation of the host animals 1-4. The bacterial oxalate transporter OxlT uptakes oxalate from the gut to bacterial cells and excrete formate as a degradation product, with a strict discrimination from other carboxylates that serve as nutrients 5-7. Nevertheless, the underlying mechanism remains unclear. Here, we present crystal structures of oxalate-bound and ligand-free OxlT in two different conformations, occluded and outward-facing states. The oxalate binding site contains two basic residues that form salt bridges with a dicarboxylate substrate while preventing the conformational switch to the occluded state without an acidic substrate, a disallowed state for an antiporter 8, 9. The occluded ligand-binding pocket can accommodate oxalate but not larger dicarboxylates, such as metabolic intermediates. The permeation pathways from the binding pocket are completely blocked by extensive interdomain hydrophobic and ionic interactions. Nevertheless, a molecular dynamics simulation showed that a flip of a single side chain neighbouring the substrate is sufficient to trigger the gate opening. The OxlT structure indicates the underlying metabolic interactions enabling favourable symbiosis at a molecular level.

biochemistry↗

bioRxiv2021

Novel System to Monitor In Vivo Neural Graft Activity After Spinal Cord Injury

Expectations for neural stem/progenitor cell (NS/PC) transplantation as a treatment for spinal cord injury (SCI) are increasing. However, whether and how grafted cells are incorporated into the host neural circuit and contribute to motor function recovery remain unknown. The aim of this project was to establish a novel non-invasive in vivo imaging system to visualize the activity of neural grafts by which we can simultaneously demonstrate the circuit-level integration between the graft and host, and the contribution of graft neuronal activity to host behaviour. We introduced Akaluc, a newly engineered luciferase, under control of a potent neuronal activity-dependent synthetic promoter, E-SARE, into NS/PCs and engrafted the cells into SCI model mice. Through the use of this system, we reveal that the activity of grafted cells was integrated with host behaviour and driven by host neural circuit inputs. This non-invasive system is expected to help elucidate the therapeutic mechanism of cell transplantation treatment for SCI and determine better therapy techniques that maximize the function of cells in the host circuit.

neuroscience↗

bioRxiv2021

Proton-mediated gating mechanism of anion channelrhodopsin-1

Anion channelrhodopsin from Guillardia theta (GtACR1) has Asp234 (3.2 [A]) and Glu68 (5.3 [A]) near the protonated Schiff base. Here we investigate mutant GtACR1s (e.g., E68Q/D234N) expressed in HEK293 cells. The influence of the acidic residues on the absorption wavelengths were also analyzed, using a quantum mechanical/molecular mechanical approach. The calculated protonation pattern indicates that Asp234 is deprotonated and Glu68 is protonated in the original crystal structures. The D234E mutation and the E68Q/D234N mutation shortens and lengthens the measured and calculated absorption wavelengths, respectively, which suggests that Asp234 is deprotonated in the wild type GtACR1. Molecular dynamics simulations show that upon mutation of deprotonated Asp234 to asparagine, deprotonated Glu68 reorients towards the Schiff base and the calculated absorption wavelength remains unchanged. The formation of the proton transfer pathway via Asp234 toward Glu68 and the disconnection of the anion conducting channel are likely a basis of the gating mechanism.

biochemistry↗

bioRxiv2021

Serotonergic neural network related to behavioral inhibition system

Rationale The tendency to avoid punishment, called behavioral inhibition system, is an essential aspect of motivational behavior. Behavioral inhibition system is related to negative affect, such as anxiety, depression and pain, but its neural basis has not yet been clarified. Objectives To clarify the association between individual variations in behavioral inhibition system and brain 5-HT2A receptor availability and specify which brain networks were involved in healthy male subjects, using [18F]altanserin positron emission tomography and resting-state functional magnetic resonance imaging. Results Behavioral inhibition system score negatively correlated with 5-HT2A receptor availability in anterior cingulate cortex. A statistical model indicated that the behavioral inhibition system score was associated with 5-HT2A receptor availability, which was mediated by the functional connectivity between anterior cingulate cortex and left middle frontal gyrus, both of which involved in the cognitive control of negative information processing. Conclusions Individuals with high behavioral inhibition system displays low 5-HT2A receptor availability in anterior cingulate cortex and this cognitive control network links with prefrontal-cingulate integrity. These findings have implications for underlying the serotonergic basis of physiologies in aversion.

neuroscience↗