Biology subjects

Kim, Y. G.

Publications and source records attributed to Kim, Y. G..

10 recordsLinked to original sources

bioRxiv2026

Value and spatial preferences guide habitual reaching and manual object selection in primates

Habits are automatic actions shaped by prior experience, enabling efficient and fast responses in stable environments. While habitual gaze rapidly directs the eyes toward valuable objects, the mechanisms underlying habitual manual choice for reaching and grasping remain unclear. Here we show that macaque monkeys develop habitual manual choices toward previously rewarded objects through multi-day object-value learning, driven by learned value and spatial preferences. This reaching habit persisted without reward and showed shorter latencies than in value-deliberative tasks, consistent with automatic control. Regression analyses further revealed that manual choice was guided by learned object values, whereas visual salience had no effect, unlike gaze habits. Instead, intrinsic spatial preferences continued to bias reaching behavior even after long-term value learning. These findings demonstrate that habitual manual choice arises from the integration of spatial preferences and long-term value memory, defining a distinct mechanism of automatic behavior beyond habitual gaze.

animal behavior and cognition↗

bioRxiv2025

Prediction of zoonotic virus-host transmissibility using comparative airway organoids

AbstractThe emergence of new pandemic zoonotic diseases is accelerating. However, current approaches to control after outbreaks often allow the epidemic or pandemic spread of new zoonotic diseases, exemplified by the case of COVID-19. Prediction of zoonotic transmissibility will help minimize the outbreaks and socioeconomic damage. Here, we established highly efficient comparative airway organoids with minimal components from a panel of mammalian species for long-term culture and passaging and validated their utility to predict the transmissibility of zoonotic pathogens. Airway organoids from each species recapitulated the airway histology and contained the major cell types in the airway. They recapitulated the known susceptibility of their host species and tissues to diverse viruses. Transcriptomic analyses revealed that organoids from susceptible species induced genes of anti-viral immune responses only in common upon exposure to the same virus, although each species organoids displayed differential gene expression profiles. Also, organoids of the same species displayed differential transcriptomic responses against different viruses but induced anti-viral immune genes only in common. Our work provides a roadmap for comprehensive species- and tissue-level organoid panels for quick and reproducible uncharacterized pathogen surveillance to predict and prevent the next pandemic.

developmental biology↗

bioRxiv2025

Stabilization of the trimeric pre-fusion structures of influenza H1 and H9 hemagglutinins by mutations in the stem helices

Stabilizing the pre-fusion structures of antigenic proteins can enhance the effectiveness of antiviral vaccines. The pre-fusion form of hemagglutinin (HA) from the influenza virus typically adopts a stable trimeric structure. However, the recombinant ectodomain of HA from the A/California/04/2009 (H1N1) influenza virus formed a monomer in solution rather than the expected trimer. To promote trimer formation in the pre-fusion conformation, we redesigned five amino acid residues in the stem region of HA that are involved in trimerization. The engineered HA protein formed a stable trimer at both pH 8.0 and pH 5.5. Additionally, the thermal stability of the modified protein improved, as indicated by an approximately ten-degree increase in its denaturation temperature. Cryo-EM analysis at 2.2 [A] resolution confirmed that the mutant HA protein adopted the pre-fusion structure. Furthermore, the stabilized mutant exhibited enhanced immunogenicity in mice. We applied the same optimization strategy to the HA proteins from A/Malaysia/1706215/2007 (H1N1) and A/swine/Hong Kong/2106/98 (H9N2). These engineered proteins demonstrated increased thermal stability and retained a trimeric pre-fusion structure, as confirmed by cryo-EM analysis. Extending this optimization strategy to the equivalent five residues in hemagglutinins from six additional group 1 influenza viruses successfully stabilized their trimeric structures.

biophysics↗

bioRxiv2024

Cerebellar systems consolidation driven by the temporal dynamics of Purkinje cell excitability

Systems consolidation, essential for long-term memory formation, orchestrates the reorganization of newly encoded memories from the cortex into subsequent neural circuitry. While the role of synaptic mechanism in consolidation is well understood, the contribution of neuronal intrinsic excitability (IE) remains relatively unexplored. Herein, we adopted the optokinetic reflex, a cerebellum-dependent learning model, and manipulated IE of the sole output of the cerebellar cortex, Purkinje cells (PCs), to corroborate the direct causality between neuronal IE and memory consolidation. Optogenetic modulation of PC-IE post-learning uncovered a critical temporal window for its role in systems consolidation. Specifically, increasing PC-IE within 90 minutes after learning disrupted memory consolidation, while outside this window, memory retention remained unaffected. Under physiological conditions, PC-IE naturally decreased during this time frame and returned to baseline thereafter. Moreover, abnormally heightened PC-IE eliminated intrinsic plasticity in flocculus-targeting neurons (FTNs) within the medial vestibular nucleus (MVN), a key downstream circuit involved in long-term memory storage. These findings highlight the precise temporal dynamics of IE as a pivotal mechanism in systems consolidation, emphasizing its vulnerability to disruptions.

neuroscience↗

bioRxiv2024

Kynurenine monooxygenase blockade reduces endometriosis-like lesions, improves visceral hyperalgia, and rescues mice from a negative behavioural phenotype in experimental endometriosis

Endometriosis is a common and debilitating neuro-inflammatory disorder that is associated with chronic pain. Definitive diagnosis is based on the presence of endometrial-like tissue (lesions) in sites outside the uterus. Kynurenine monooxygenase (KMO) is a mitochondrial enzyme of tryptophan metabolism that regulates inflammation and immunity. Here, we show that KMO is expressed in epithelial cells in human endometriosis tissue lesions and in corresponding lesions in a mouse model of endometriosis. In mice, oral treatment with the potent KMO inhibitor KNS898 induced a biochemical state of KMO blockade with accumulation of kynurenine, diversion to kynurenic acid and ablation of 3-hydroxykynurenine production. In the mouse model of endometriosis, KMO inhibition improved histological outcomes and endometriosis pain-like behaviours, even when KNS898 treatment commenced one week after initiation of lesions. Taken together, these results suggest that KMO blockade is a promising new non-hormonal therapeutic modality for endometriosis.

pathology↗

bioRxiv2023

Hypothalamic neuronal activation in primates drives naturalistic goal-directed eating behavior

Eating addiction is the primary cause of modern obesity. Although the causal role of the lateral hypothalamic area (LHA) for eating is demonstrated in rodents, there is no evidence in primates regarding naturalistic eating behaviors. We investigated the role of LHA GABAergic (LHAGABA) neurons in eating by chemogenetics in three macaques. LHAGABA neuron activation significantly increased naturalistic goal-directed behaviors and food motivation, which was specific for palatable food. PET and MRS validated the chemogenetic activation. Rs-fMRI result revealed that functional connectivity (FC) between the LHA and frontal areas was increased, while the FC between the frontal cortices was decreased after the LHAGABA neuron activation. Thus, our study elucidates the role of LHAGABA neurons in eating and obesity therapeutics for primates and humans.

neuroscience↗

bioRxiv2021

Minhee Analysis Package: An Integrated Software Package for Detection and Management of Spontaneous Synaptic Events

To understand the information encoded in a connection between the neurons, postsynaptic current (PSC) has been widely measured as a primary index of synaptic strength in the field of neurophysiology. Although several automatic detection methods for PSCs have been proposed to simplify a workflow in the analysis, repetitive steps such as quantification and management of PSC data should be still performed with much effort. Here, we present Minhee Analysis Package, an integrated standalone software package that is capable of detecting, sorting, and quantifying PSC data. First, we developed a stepwise exploratory algorithm to detect PSC and validated our detection algorithm using the simulated and experimental data. We also described all the features and examples of the package so that users can use and follow them properly. In conclusion, our software package is expected to improve the convenience and efficiency of neurophysiologists to analyze PSC data by simplifying the workflow from detection to quantification. Minhee Analysis Package is freely available to download from http://www.github.com/parkgilbong/Minhee_Analysis_Pack.

neuroscience↗

bioRxiv2020

Ablation of STAT3 in Purkinje Cells Reorganizes Cerebellar Synaptic Plasticity in Long-Term Fear Memory Network

Emotional memory processing, such as fear memory, engages a large neuronal network of brain regions including the cerebellum. However, the molecular and cellular mechanisms of the cerebellar cortex modulating the fear memory network is largely unknown. Here, we illustrate a novel mechanism by which synaptic signaling in cerebellar Purkinje cells (PCs) via STAT3 regulates long-term fear memory. Firstly, we generated PC-specific STAT3 knockout (STAT3PKO) mice. Transcriptome analyses revealed that STAT3 deletion results in transcriptional changes that lead to an increase in the expression of glutamate receptors. The amplitude of AMPA receptor-mediated excitatory postsynaptic currents at parallel fiber to PC synapses was larger in STAT3PKO mice than in wild-type littermates. Conditioning at the parallel fiber induced long-term depression of parallel fiber-PC synapses in STAT3PKO mice while the same manipulation induced long-term potentiation in wild-type littermates. Interestingly, STAT3PKO mice showed an aberrantly enhanced long-term fear memory. Neuronal activity in fear-related regions increased in fear-conditioned STAT3PKO mice. Our data suggest that STAT3-dependent molecular regulation in PCs is indispensable for proper expression of fear memory processing.

neuroscience↗

bioRxiv2020

Impaired hand dexterity function in a non-human primate model with chronic Parkinson's disease

Symptoms of Parkinsons disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed an alteration in Parkinsonian tremor symptoms, loss of dopaminergic neuron, and positron emission tomography (PET) imaging of dopamine transporters (DAT) in these models. HDT latency significantly increased in NHP-PD models. In addition, a significant inverse correlation between HDT and DAT was identified, but no local bias was found. The correlation with intention tremor symptoms was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

neuroscience↗

bioRxiv2020

Gait analysis of healthy rhesus monkeys using a pressure-sensing walkway system

Gait analysis in non-human primate models has been performed to elucidate the neural systems involved in controlling quadrupedal locomotor behavior. This study aimed to use a pressure-sensing walkway to identify characteristics of species-specific quadrupedal locomotion in rhesus monkeys. A total of nine healthy adult female rhesus monkeys (Macaca mulatta) were used for gait analysis. We measured the temporo-spatial and kinetic parameters of quadrupedal gait using a custom-built pressure-sensing walkway and compared the left- and right-side parameters to assess the symmetry of the gait pattern. All temporo-spatial and kinetic parameter values showed no significant differences among the nine rhesus monkeys for both the forelimbs and hindlimbs. However, significant differences were observed between forelimb and hindlimb kinetic parameters such as peak vertical force, vertical impulse, and the percentage of body weight distribution. All kinetic parameter values were higher for the forelimbs than for the hindlimbs. These data indicated that the center of gravity in healthy rhesus monkeys is located at the forelimbs rather than at the hindlimbs while walking. Furthermore, the symmetry indices considered for symmetric gait pattern showed a low variability. Most median symmetry index values were nearly zero, indicating no difference between the right and left sides. This study described valid methods for assessing gait parameters and demonstrated rhesus-specific characteristics of quadrupedal locomotion, providing a basis for the assessment of gait normality in rhesus monkeys.

animal behavior and cognition↗