Biology subjects

Kim, S.-G.

Publications and source records attributed to Kim, S.-G..

At least 19 recordsLinked to original sources

bioRxiv2026

Descending somatosensory and motor cortical inputs shape auditory processing in the midbrain

Integrating multisensory and behavioral information is essential for sensory perception. In the auditory system, multisensory and behavioral influences emerge early in subcortical structures. Descending projections from non-auditory cortical areas are well positioned to convey such signals, yet how they shape subcortical auditory processing remains poorly understood. Here, we investigated corticocollicular projections from the primary somatosensory (S1) and motor (M1) cortices to the inferior colliculus (IC), a principal integration center in the auditory midbrain. We found that trunk- and limb-related regions of S1 and M1 form prominent monosynaptic projections to the IC, and that optogenetic activation of these projections robustly drives IC activity. Notably, a substantial population of cortical-responsive neurons did not respond to sound. In sound-responsive neurons, concurrent cortical stimulation enhanced sound-evoked responses, whereas cortical activation preceding sound onset suppressed them. Furthermore, both cortical-responsive IC neurons and deep-layer S1 and M1 neurons exhibited locomotion-related modulation and anticipatory activity prior to movement onset, suggesting that these descending pathways convey movement-related signals to the IC. Together, our findings identify a descending sensorimotor circuit that integrates body- and movement-related information with auditory processing in the auditory midbrain.

neuroscience↗

bioRxiv2026

Pitch motor areas contribute to the perception of prosodic categories in speech

Prosody is a fundamental aspect of speech characterized by suprasegmental features such as pitch. Prosodic pitch contours are used to convey speakers intentions, for example, to make a statement or ask a question. Understanding these intentions requires abstracting continuous, variable pitch information into discrete categories. Category perception has been proposed to recruit the motor system in an effector-specific manner, whereby cortical areas controlling motor effectors support speech sound recognition by identifying articulatory gestures. However, it remains unclear whether effectors involved in pitch production similarly contribute to prosodic category perception. To address this question, we collected magnetoencephalography data from 29 participants (15 females) while they first sang pitches arranged in five-tone melodies and then identified the prosody (Statement vs. Question) of single words varying in pitch contour along a five-level continuum. Using a region-restricted searchlight approach to decode singing from rest, we localized two premotor regions for pitch production, corresponding to the ventral and dorsal laryngeal motor cortex (LMC). A separate neural decoding analysis revealed that perceived prosodic categories were decodable in these regions, especially from the dorsal LMC that is more closely associated with pitch regulation. Importantly, decoding performance mirrored behavioral discriminability of prosodic categories across the continuum, suggesting that these regions are involved in perceptual decision-making. Finally, pitch motor areas exchanged category-related information with auditory regions, indicating these areas do not merely echo the processing in auditory regions. Together, these findings highlight effector-specific motor support for prosodic category perception, thereby broadening our understanding of motor involvement in speech perception. Significance StatementSpeech perception has been proposed to recruit the premotor cortex, with different subregions linking speech sounds to the articulatory gestures used to produce them. We investigated this idea through prosody--pitch changes in speech conveying meanings such as statements and questions. Using magnetoencephalography, we identified pitch motor areas during a singing task and tested whether they represent perceived prosodic categories. We found that prosodic categories were distinguishable in these regions and that this neural discriminability mirrored behavioral discriminability across clear and ambiguous prosody, suggesting involvement in perceptual decision-making. These findings are unlikely to reflect passive echoes from auditory regions, as pitch motor areas actively influenced them during categorical processing. Our results highlight effector-specific motor support for forming abstract prosodic representations.

neuroscience↗

bioRxiv2026

Deafness rapidly reorganizes functional brain networks in adult mice

Sensory loss triggers crossmodal reorganization across sensory modalities, and accumulating evidence indicates that this adaptive capacity persists into adulthood. However, the global organizing principles of such plasticity remain poorly understood, as conventional animal model approaches do not permit longitudinal, whole-brain measurements. Here, we use ultra-high-field (15.2T) BOLD fMRI to map deafening-induced functional reorganization across the entire brain in young adult mice. Within one week of deafening, the auditory cortex is recruited by somatosensory and visual inputs, while stimulus-evoked responses are potentiated in the spared sensory pathways. Reorganization extends beyond sensory cortices to higher-order association areas, including anterior cingulate, retrosplenial, and posterior parietal cortices. Resting-state fMRI further reveals strengthened coupling both within sensory systems and between sensory systems and a default mode-like network. These findings demonstrate that adult-onset deafness rapidly reorganizes functional brain networks and further implicate the default mode-like network as a potential mediator of crossmodal integration.

neuroscience↗

bioRxiv2026

4-Hexylresorcinol Enhances Skeletal Muscle Glucose Handling through the AMPK-GLUT4 axis in Diabetic Rats

BackgroundSkeletal muscle insulin resistance in diabetes is characterized by impaired GLUT4 availability and dysregulated AMP-activated protein kinase (AMPK) signaling. We investigated whether 4-hexylresorcinol (4HR) modulates glucose metabolism and AMPK-acetyl-CoA carboxylase (ACC)-GLUT4 signaling in vitro and in streptozotocin (STZ)-induced diabetic rats. MethodsDifferentiated C2C12 myotubes were treated with 4HR (0.1-10 {micro}M) and assessed for glucose uptake, GLUT4 translocation, protein stability, proteasome involvement, and AMPK/ACC phosphorylation. In vivo, streptozotocin (STZ)-induced diabetic rats received subcutaneous 4HR (10 mg{middle dot}kgL{superscript 1}, 5 times/week for 7 weeks). Glycemic control, insulin secretion, muscle glycogen content, and serum protein profiles were evaluated. Results4HR markedly increased glucose uptake (>5-fold vs. control, p<0.05), accompanied by increased phosphorylation of AMPK (Thr172) and ACC (Ser79), and redistribution of GLUT4 toward the cell periphery. Cycloheximide chase and proteasome inhibition experiments indicated partial stabilization of GLUT4. In diabetic rats, 4HR reduced fasting glycemia, improved glucose tolerance, elevated circulating insulin, and restored glycogen-rich fibers in skeletal muscle. Serum profiling revealed a metabolic and anti-inflammatory shift, with increased AMPK, p-ACC, GLUT1, LGR4, LDHA, and PGC-1, alongside suppression of NF-{kappa}B and TNF-. Conclusion4HR improves skeletal muscle glucose metabolism in STZ-induced diabetes, associated with activation of AMPK-ACC signaling, preservation of GLUT4 expression, and restoration of glycogen content. These findings highlight 4HR as a promising candidate for further investigation in diabetic muscle dysfunction and metabolic disease.

molecular biology↗

bioRxiv2025

Longitudinal Resting-State fMRI of Awake Mice During Habituation: Stress, Head Motion, and Functional Connectivity

Awake mouse fMRI is a powerful tool for both neuroscience and translational research. To minimize head motion during scanning, habituation under physical restraint is commonly used. However, it remains unclear how stress levels and head motion evolve during habituation, particularly within the MRI environment. To address this, we repeatedly measured plasma corticosterone (CORT) levels in three groups of mice - controls, mice habituated outside the MRI magnet, and mice habituated within the fMRI environment - and acquired longitudinal resting-state fMRI data daily during an eight-day habituation period and again 15 days post-habituation at 15.2 T. We found that CORT levels initially increased by approximately twofold and gradually decreased during habituation outside the magnet, whereas in mice habituated within the fMRI environment, CORT levels increased two- to fourfold and remained elevated throughout the habituation period. One week after habituation, CORT levels returned to baseline in both groups. Throughout all resting-state fMRI scanning sessions, head motion and functional connectivity remained stable, likely due to the well-designed restraint cradle that permitted paw movement. These results suggest that additional habituation days do not further reduce stress, provided that head motion remains within acceptable limits.

neuroscience↗

bioRxiv2025

Reverse Double-Dipping: When Data Dips You, Twice--Stimulus-Driven Information Leakage in Naturalistic Neuroimaging

This article elucidates a methodological pitfall of cross-validation for evaluating predictive models applied to naturalistic neuroimaging data---namely, "stimulus-driven leakage." While this problem has been well known as "leakage in training examples" in machine learning, it may be difficult to detect in practice due to conventions in neuroscience. Stimulus-driven leakage can occur when predictive modelling is applied to data from a conventional neuroscientific design, characterized by a limited set of stimuli repeated across trials and/or participants. It results in spurious predictive performance due to overfitting to repeated signals, even in the presence of independent noise. Through comprehensive simulations and real-world examples, following a theoretical formulation, the article underscores how such data leakage can occur and how severely it can compromise results and conclusions when combined with widely spread informal reverse inference. The article concludes with practical recommendations for researchers to avoid stimulus-driven leakage in their experimental design and analysis.

neuroscience↗

bioRxiv2025

Shared and distinct representational dynamics of phonemes and prosody in ventral and dorsal speech streams

Phonemes and prosodic contours are fundamental elements of speech used to convey complementary meanings. Perceiving these elements requires mapping variable acoustic cues onto discrete categories along ventral and dorsal speech streams. While traditional models make clear predictions, exactly where and when this acoustic-to-categorical mapping occurs remains unclear. Using magnetoencephalography and behavioural psychophysics, combined with time-resolved representational similarity and multivariate transfer entropy analyses, we show how phonemes and prosody propagate along the dual streams and how their categorical representations are gradually formed. Contrary to theoretical predictions, acoustic and categorical representations occur in parallel, rather than serially, across time and space for both elements. Moreover, prosody categories extend further along both streams than phoneme categories, with differently weighted contributions of posterior temporal areas. These results highlight a shared principle of parallel acoustic and categorical processing, yet partially distinct abstraction mechanisms for phonemes and prosody, key to access the multilayered meaning of speech.

neuroscience↗

bioRxiv2024

Encoding opposing valences through frequency-dependent transmitter switching in single peptidergic neurons

Peptidergic neurons often co-express fast transmitters and neuropeptides in separate vesicles with distinct release properties. However, the release dynamics of each transmitter in various contexts have not been fully understood in behaving animals. Here, we demonstrate that calcitonin gene-related peptide (CGRP) neurons in the external lateral subdivision of the parabrachial nucleus (CGRPPBel) encode opposing valence via differential release, rather than corelease, of glutamate and neuropeptides, according to firing rate. Glutamate is released preferentially at lower firing rates with minimal release at higher firing rates, whereas neuropeptides are released at higher firing rates, resulting in frequency-dependent switching of transmitters. Aversive stimuli evoke high frequency responses with accompanying neuropeptide release to encode negative valence, whereas appetitive stimuli evoke low frequency responses with glutamate release to encode positive valence. Our study reveals a previously unknown capability of single CGRPPBel neurons to bidirectionally encode valence via frequency-dependent differential release of transmitters in vivo.

neuroscience↗

bioRxiv2024

Inositol polyphosphate multikinase regulates Th1 and Th17 cell differentiation by controlling Akt-mTOR signaling

Activated proinflammatory T helper (Th) cells, such as Th1 and Th17 cells, mediate immune responses against intra- and extra-cellular pathogens as well as cause the development of various autoimmune diseases. Inositol polyphosphate multikinase (IPMK) is a key enzyme essential for inositol phosphate and phosphoinositide metabolism, which is known to control major biological events such as growth; however, its role in the function of Th cells remains unclear. Here we show that the expression of IPMK is highly induced in distinct Th1 and Th17 subsets. Further, while conditional deletion of IPMK in CD4+ T cells is dispensable for Th2-dependent immune responses, both Th1- and Th17-mediated immune responses are markedly diminished when this enzyme is absent resulting in reduced resistance to Leishmania major infection and attenuation of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. In addition, IPMK-deficient naive CD4+ T cells display aberrant T cell activation and impaired differentiation into Th17 cells, which is associated with reduced activation of Akt, mechanistic target of rapamycin (mTOR), and STAT3. Mechanistically, IPMK as a phosphatidylinositol 3-kinase (PI3-kinase) controls the production of phosphatidylinositol (3,4,5)-trisphosphate, thereby promoting T cell activation, differentiation, and effector functions. Our findings suggest that IPMK acts as a critical regulator of Th1 and Th17 differentiation, highlighting the physiological importance of IPMK in Th1- and Th17-mediated immune homeostasis.

immunology↗

bioRxiv2023

Non-Invasive Perfusion Imaging of the Human Brain via Breath-Holding: A DSC MRI Study

Dynamic susceptibility contrast (DSC) MRI plays a pivotal role in the accurate diagnosis and prognosis of several neurovascular diseases, but is limited by its reliance on gadolinium, an intravascularly injected chelated metal. Here, we determined the feasibility of measuring perfusion using a DSC analysis of breath-hold-induced gradient-echo-MRI signal changes. We acquired data at both 3T and 7T from ten healthy participants who engaged in eight consecutive breath-holds. By pairing a novel arterial input function strategy with a standard DSC MRI analysis, we measured the cerebral blood volume, flow, and transit delay, and found values to agree with those documented in the literature using gadolinium. We also observed voxel-wise agreement between breath-hold and arterial spin labeling measures of cerebral blood flow. Breath-holding resulted in significantly higher contrast-to-noise (6.2 at 3T vs 8.5 at 7T) and gray matter-to-white matter contrast at higher field strength. Finally, using a simulation framework to assess the effect of dynamic vasodilation on perfusion estimation, we found global perfusion underestimation of 20-40%. For the first time, we have assessed the feasibility of and limitations associated with using breath-holds for perfusion estimation with DSC. We hope that the methods and results presented in this study will help pave the way toward contrast-free perfusion imaging, in both basic and clinical research.

biophysics↗

bioRxiv2023

Genome assembly of Hibiscus sabdariffa L. provides insights into biosynthetic pathways of medicinal natural products

Hibiscus sabdariffa L. is a widely cultivated herbaceous plant with diverse applications in food, tea, fiber, and medicine. In this study, we present a high-quality genome assembly of H. sabdariffa using more than 33 Gbps of high-fidelity (HiFi) long-read sequencing data at 20X coverage. The primary assembly and haplotype-resolved genomes exhibit an N50 contig length of 26.25 Mbps, 11.96 Mbps, and 14.50 Mbps, with a coverage of 141.3%, 86.0%, and 88.6%, respectively. By aligning 26 Gbps of total RNA sequencing data (PE100) extracted from leaves, we predicted 154k, 79k, and 87k genes in the respective genome. The completeness of the genomes and predicted genes was confirmed by benchmarking universal single-copy orthologs analysis on a eudicots_odb10 database, with a 99.3% complete rate for the primary assembly. The high-quality genome resource allowed the construction of genetic networks for phenylpropanoid and flavonoid metabolism, thereby facilitating the identification of candidate genes involved in the biosynthesis of key intermediates for roselle-specific medicinal natural products. Comprehensive genomic and functional analysis opens avenues for further exploration and application of valuable natural products derived from H. sabdariffa.

genomics↗

bioRxiv2023

No Replication of Direct Neuronal Activity-related (DIANA) fMRI in Anesthetized Mice

Direct imaging of neuronal activity (DIANA) by fMRI could be a revolutionary approach for advancing systems neuroscience research. To independently replicate this observation, we performed fMRI experiments in anesthetized mice. The BOLD response to whisker stimulation was reliably detected in the primary barrel cortex before and after DIANA experiments; however, no direct neuronal activity-like fMRI peak was observed in data of individual animals with the 50-300 trials. Extensively averaged data involving 1,050 trials in 6 mice showed a flat baseline and no detectable neuronal activity-like fMRI peak. However, spurious, non-replicable peaks were found when using a small number of trials, and artifactual peaks were detected when some outlier-like trials were excluded. Further, no detectable DIANA peak was observed in the BOLD-responding thalamus from the selected trials with the neuronal activity-like reference function in the barrel cortex. Thus, we were unable to replicate the previously reported results without data pre-selection.

neuroscience↗

bioRxiv2023

READRetro: Natural Product Biosynthesis Planning with Retrieval-Augmented Dual-View Retrosynthesis

Elucidating the biosynthetic pathways of natural products has been a major focus of biochemistry and pharmacy. However, predicting the whole pathways from target molecules to metabolic building blocks remains a challenge. Here we propose READRetro as a practical bio-retrosynthesis tool for planning the biosynthetic pathways of natural products. READRetro effectively resolves the tradeoff between generalizability and memorability in bio-retrosynthesis by implementing two separate modules; each module is responsible for either generalizability or memorability. Specifically, READRetro utilizes a rule-based retriever for memorability and an ensemble of two dual-representation-based deep learning models for generalizability. Through extensive experiments, READRetro was demonstrated to outperform existing models by a large margin in terms of both generalizability and memorability. READRetro was also capable of predicting the known pathways of complex plant secondary metabolites such as monoterpene indole alkaloids, demonstrating its applicability in the real-world bio-retrosynthesis planning of natural products. A website (https://readretro.net) and open-source code have been provided for READRetro, a practical tool with state-of-the-art performance for natural product biosynthesis research.

bioinformatics↗

bioRxiv2022

Whole-brain mapping of effective connectivity by fMRI with cortex-wide patterned optogenetics

Functional magnetic resonance imaging (fMRI) with optogenetic neural manipulation is a powerful tool that enables brain-wide mapping of effective functional networks. To achieve flexible manipulation of neural excitation throughout the mouse cortex, we incorporated spatiotemporal programmable optogenetic stimuli generated by a digital micromirror device into an MR scanner via an optical fiber bundle for the first time. This approach offered versatility in space and time in planning the photostimulation pattern, combined with in situ optical imaging and cell-type or circuit-specific genetic targeting in individual mice. Brain-wide effective connectivity obtained by fMRI with optogenetic stimulation of atlas-based cortical regions is generally congruent with anatomically defined axonal tracing data but is affected by the types of anesthetics that act selectively on specific connections. fMRI combined with flexible optogenetics opens a new path to investigate dynamic changes in functional brain states in the same animal through high-throughput brain-wide effective connectivity mapping.

neuroscience↗

bioRxiv2022

Post-weaning parvalbumin expression in left orbitofrontal cortex shapes sociability in female mice

The adolescent social experience is essential for the maturation of the prefrontal cortex in mammalian species. However, it still needs to be determined which cortical circuits mature with such experience and how it shapes adult social behaviors in a sex-specific manner. Here, we examined social approaching behaviors in male and female mice after post-weaning social isolation (PWSI), which deprives social experience during adolescence. We found that the PWSI, particularly isolation during late adolescence, caused an abnormal increase in social approaches (hypersociability) only in female mice. We further found that the PWSI female mice showed reduced parvalbumin (PV) expression in the left orbitofrontal cortex (OFCL). When we measured neural activity in the female OFCL, a substantial number of neurons showed higher activity when mice sniffed other mice (social sniffing) than when they sniffed an object (object sniffing). Interestingly, the PWSI significantly reduced both the number of activated neurons and the activity level during social sniffing in female mice. Similarly, the CRISPR/Cas9-mediated knock-down of PV in the OFCL during late adolescence enhanced sociability and reduced the social sniffing-induced activity in adult female mice via decreased excitability of PV+ neurons and reduced synaptic inhibition in the OFCL. Moreover, optogenetic activation of excitatory neurons or optogenetic inhibition of PV+ neurons in the OFCL enhanced sociability in female mice. Our data demonstrate that the adolescent social experience is critical for the maturation of PV+ inhibitory circuits in the OFCL; this maturation shapes female social behavior via enhancing social representation in the OFCL. Significance StatementAdolescent social isolation often changes adult social behaviors in mammals. Yet, we do not fully understand the sex-specific effects of social isolation and the brain areas and circuits that mediate such changes. Here, we found that adolescent social isolation causes three abnormal phenotypes in female but not male mice: hypersociability, decreased PV+ neurons in the OFCL, and decreased socially evoked activity in the OFCL. Moreover, PV deletion in the OFCL in vivo caused the same phenotypes in female mice by increasing excitation compared with inhibition within the OFCL. Our data suggest that adolescent social experience is required for PV maturation in the OFCL, which is critical for evoking OFCL activity that shapes social behaviors in female mice.

animal behavior and cognition↗

bioRxiv2021

Dissection of brain-wide spontaneous and functional somatosensory circuits by fMRI with optogenetic silencing

To further advance functional magnetic resonance imaging (fMRI)-based brain science, it is critical to dissect fMRI activity at the circuit level. To achieve this goal, we combined brain-wide fMRI with neuronal silencing in well-defined regions. Since focal inactivation suppresses excitatory output to downstream pathways, intact input and suppressed output circuits can be separated. Highly specific cerebral blood volume-weighted fMRI was performed with optogenetic simulation of local GABAergic neurons in mouse somatosensory regions. Brain-wide spontaneous somatosensory networks were found mostly in ipsilateral cortical and subcortical areas, which differed from the bilateral homotopic connections commonly observed in resting-state fMRI data. The evoked fMRI responses to somatosensory stimulation in regions of the somatosensory network were successfully dissected, allowing the relative contributions of spinothalamic (ST), thalamocortical (TC), corticothalamic (CT), corticocortical (CC) inputs and local intracortical circuits to be determined. The ventral posterior thalamic nucleus (VPL) receives ST inputs, while the posterior medial thalamic nucleus (POm) receives CT inputs from the primary somatosensory cortex (S1) with TC inputs. The secondary somatosensory cortex (S2) receives mostly direct CC inputs from S1 and a few TC inputs from the VPL. The TC and CC input layers in cortical regions were identified by laminar-specific fMRI responses with a full width at half-maximum of <150 {micro}m. Long-range synaptic inputs in cortical areas were amplified approximately 2-fold by local intracortical circuits, which is consistent with electrophysiological recordings. Overall, whole-brain fMRI with optogenetic inactivation revealed brain-wide, population-based long-range circuits, which could complement data typically collected in conventional microscopic functional circuit studies.

neuroscience↗

bioRxiv2021

Linguistic modulation of the neural encoding of phonemes

Speech comprehension entails the neural mapping of the acoustic speech signal onto learned linguistic units. This acousto-linguistic transformation is bi-directional, whereby higher-level linguistic processes (e.g., semantics) modulate the acoustic analysis of individual linguistic units. Here, we investigated the cortical topography and linguistic modulation of the most fundamental linguistic unit, the phoneme. We presented natural speech and phoneme quilts (pseudo-randomly shuffled phonemes) in either a familiar (English) or unfamiliar (Korean) language to native English speakers while recording fMRI. This allowed us to dissociate the contribution of acoustic vs. linguistic processes towards phoneme analysis. We show that (1) the acoustic analysis of phonemes is modulated by linguistic analysis and (2) that for this modulation both of acoustic and phonetic information need to be incorporated. These results suggest that the linguistic modulation of cortical sensitivity to phoneme classes minimizes prediction error during natural speech perception, thereby aiding speech comprehension in challenging listening situations.

neuroscience↗

bioRxiv2021

Single-cell RNA-sequencing of Nicotiana attenuata petal cells reveals the entire biosynthetic pathway of a floral scent

High-throughput single-cell RNA sequencing (scRNA-seq) identifies distinct cell populations based on cell-to-cell heterogeneity in gene expression. By examining the distribution of the density of gene expression profiles, the metabolic features of each cell population can be observed. Here, we employ the scRNA-seq technique to reveal the entire biosynthetic pathway of a flower volatile. The corolla (petals) of the wild tobacco Nicotiana attenuata emits a bouquet of scents that are composed mainly of benzylacetone (BA), a rare floral volatile. Protoplasts from the N. attenuata corolla were isolated at three different time points, and the transcript levels of >16,000 genes were analyzed in 3,756 single cells. We performed unsupervised clustering analysis to determine which cell clusters were involved in BA biosynthesis. The biosynthetic pathway of BA was uncovered by analyzing gene co-expression in scRNA-seq datasets and by silencing candidate genes in the corolla. In conclusion, the high-resolution spatiotemporal atlas of gene expression provided by scRNA-seq reveals the molecular features underlying cell-type-specific metabolism in a plant.

plant biology↗