Biology subjects

Chung, W.-S.

Publications and source records attributed to Chung, W.-S..

12 recordsLinked to original sources

bioRxiv2026

Long-range neural pathways for octopus chemotactile processing revealed from periphery-to-brain by centimeter-field microCT

Understanding how nervous systems mediate responses to sensation requires whole-body maps of periphery-to-brain connections. Octopuses exemplify this challenge with distributed control of eight arms and hundreds of suckers, yet their long-range microanatomical wiring remains elusive due to limitations in microscopy. We extend histotomography (Ding et al. 2019), a form of soft tissue microCT customized for volumetric characterization of cells and tissues, to centimeter range with a custom micro-CT imaging system (Ding et al., 2019). With its 10-mm field of view and 0.7-{micro}m isotropic voxels we created a high-resolution digital intact small octopus. This multi-tissue 3D blueprint enabled us to (i) elucidate previously uncharacterized chemotactile pathways from the suckers to the brain, (ii) discern subdivisions of the nerve ring connecting neighboring arms, and (iii) segment over 300 structures across organ systems at histology-like resolution. We release the labeled interactive digital specimen to facilitate collaborative whole-organism phenotyping as a practical foundation for digital organismal biology. ONE-SENTENCE SUMMARYWhole-body 3D histology reveals neural and organ architecture throughout a small octopus.

systems biology↗

bioRxiv2025

Mapping the nervous system of the Idiosepius hallami pygmy squid: insights from whole-animal X-ray nanotomography imaging.

The study of a nervous system as big as the cephalopods requires multimodal imaging approaches capable of capturing neural architecture across scales. Here, we present a whole-animal volume of the pygmy squid hatchling Idiosepius hallami, acquired using X-ray holographic nanotomography at the beamline ID16A of the European Synchrotron. The reconstructed 3D volume comprises 40 tiled scans acquired at a voxel size of 125 nm. While individual neurons are not resolved at this resolution, we segmented major body regions and mapped the large-scale connectivity by tracing afferent and efferent nerve bundles, including projections from the olfactory organs, chromatophore lobes, and arm ganglia to the brain. The acquisition of this dataset represents a significant milestone for X-ray nanotomography, being the largest whole animal volume imaged at this spatial resolution. The volume serves as a resource for comparative neuroscience and cephalopod biology.

neuroscience↗

bioRxiv2024

Detrimental Influence of Arginase-1 in Infiltrating Macrophages on Post-Stroke Functional Recovery and Inflammatory Milieu

Post-stroke inflammation critically influences functional outcomes following ischemic stroke. Arginase-1 (Arg1) is conventionally understood as a marker for anti-inflammatory macrophages, associated with the resolution of inflammation and promotion of tissue repair in various pathological conditions. However, its specific role in post-stroke recovery remains to be elucidated. This study investigates the functional impact of Arg1 expressed in macrophages on post-stroke recovery and inflammatory milieu. We observed a time-dependent increase in Arg1 expression, peaking at 7 days after photothrombotic stroke in mice. Cellular mapping analysis revealed that Arg1 was predominantly expressed in LysM-positive infiltrating macrophages. Using a conditional knockout (cKO) mouse model, we examined the role of Arg1 expressed in infiltrating macrophages. Contrary to its presumed beneficial effects, Arg1 cKO in LysM-positive macrophages significantly improved skilled forelimb motor function recovery after stroke. Mechanistically, Arg1 cKO attenuated fibrotic scar formation, enhanced peri-infarct remyelination, and increased synaptic density while reducing microglial synaptic elimination in the peri-infarct cortex. Gene expression analysis of FACS-sorted microglia revealed decreased TGF-{beta} signaling and pro-inflammatory cytokine activity in peri-infarct microglia from Arg1 cKO animals. In vitro co-culture experiments demonstrated that Arg1 activity in macrophages modulates microglial synaptic phagocytosis, providing evidence for macrophage-microglia interaction. These findings provide new insights into Arg1 function in CNS injury and highlight an interaction between infiltrating macrophages and resident microglia in shaping the post-stroke inflammatory milieu. Our study identifies Arg1 in macrophages as a potential therapeutic target for modulating post-stroke inflammation and improving functional recovery.

neuroscience↗

bioRxiv2024

Selective regulation of corticostriatal synapses by astrocytic phagocytosis

In the adult brain, neural circuit homeostasis depends on the constant turnover of synapses via astrocytic phagocytosis mechanisms. However, it remains unclear whether this process occurs in a circuit-specific manner. Here, we reveal that astrocytes target and reorganize excitatory synapses in the striatum. Using model mice lacking astrocytic phagocytosis receptors in the dorsal striatum, we found that astrocytes constantly remove corticostriatal synapses rather than thalamostriatal synapses. This preferential elimination suggests that astrocytes play a selective role in modulating corticostriatal plasticity and functions via phagocytosis mechanisms. Supporting this notion, corticostriatal long-term potentiation (LTP) and the early phase of motor sequence learning are dependent on astrocytic phagocytic receptors. Together, our findings demonstrate that astrocytes contribute to the connectivity and plasticity of the striatal circuit by preferentially engulfing a specific subset of excitatory synapses within brain regions innervated by multiple excitatory sources.

neuroscience↗

bioRxiv2024

Hypoxia disrupts circadian rhythms in astrocytes and causes synapse engulfment defects

Astrocytes are emerging as key regulators of neuronal synaptic network maturation and function, through control of synaptic pruning. This is important, because individuals with ASD have excess glutamatergic synapses in the cortex, but the biological mechanisms underlying this phenotype remain unclear. Here, we used human cortical organoids (hCO) derived from induced pluripotent stem cells (hiPSCs), to examine the effect of hypoxia on synapse engulfment in human astrocytes at postnatal-equivalent stages of development. We identified that hypoxia significantly inhibits the synaptosome phagocytosis, and that this phenotype is mediated through disruptions in the astrocytic circadian rhythm molecular pathway and subsequent decreased expression of MEGF10. Lastly, we demonstrated that circadian clock disruptions are sufficient to induce these observed phenotypes even in the absence of hypoxia, both in hCOs and within the mouse hippocampus in vivo. Our study uncovers a novel mechanistic link between hypoxia, circadian rhythms disruptions, and synapse pruning by astrocytes, and provides insight into the pathophysiology of ASD, and other neuropsychiatric diseases. Separately, the demonstration of the presence of circadian rhythms in hCOs opens an unprecedented opportunity to dissect the role of circadian clocks in normal brain development and how it contributes to specific diseases of environmental or genetic origin.

neuroscience↗

bioRxiv2022

Anemonefish have finer color discrimination in the ultraviolet

In many animals, ultraviolet (UV) vision guides navigation, foraging, and communication, but few studies have addressed the contribution of UV vision to color discrimination, or behaviorally assessed UV discrimination thresholds. Here, we tested UV-color vision in an anemonefish (Amphiprion ocellaris) using a novel five-channel (RGB-V-UV) LED display designed to test UV perception. We first determined that the maximal sensitivity of the A. ocellaris UV cone was at [~]386 nm using microspectrophotometry. Three additional cone spectral sensitivities had maxima at [~]497, 515, and [~]535 nm, which together informed the modelling of the fishs color vision. Anemonefish behavioral discrimination thresholds for nine sets of colors were determined from their ability to distinguish a colored target pixel from grey distractor pixels of varying intensity. We found that A. ocellaris used all four cones to process color information and is therefore tetrachromatic, and fish were better at discriminating colors (i.e., color discrimination thresholds were lower, or more acute) when targets had UV chromatic contrast elicited by greater stimulation of the UV cone relative to other cone types. These findings imply that a UV component of color signals and cues improves their detectability, that likely increases the salience of anemonefish body patterns used in communication and the silhouette of zooplankton prey.

animal behavior and cognition↗

bioRxiv2022

Multiple rod layers increase the speed and sensitivity of vision in nocturnal reef fishes

Multibank retinas have rod photoreceptors stacked into multiple layers. They are found in many species of fish that inhabit dim environments and are one of the most common visual adaptations in the deep-sea. Despite its prevalence, the function of multibank retinas remained unknown. Two predominant theories, neither of which has been tested, have emerged: 1) they enhance sensitivity in dim light, and 2) they allow colour vision in dim light. To investigate the sensitivity hypothesis, we performed electrophysiological recordings and compared the rod pigments of three species of nocturnal reef fishes, two with a multibank retina (Neoniphon sammara and Myripristis violacea) and a control species with a single rod bank (Ostorhinchus compressus). Results indicated that nocturnal reef fishes with a multibank retina have higher temporal resolution of vision, as indicated by electrophysiology, and that their rhodopsin proteins likely also have faster retinal release kinetics, as suggested by amino acid substitutions. Electrophysiology also showed that the multibank retina conferred greater sensitivity to both dim and bright intensities than a single rod bank and this occurred at times when rod-derived signals usually dominate the visual response. This study provides the first functional evidence for enhanced dim-light sensitivity using a multibank retina while also suggesting novel roles for the adaptation in enhancing bright-light sensitivity and the speed of vision. SignificanceMost vertebrates have one layer of the dim-light active rod photoreceptors; however, some species have multiple layers, known as a multibank retina. We used electrophysiology on nocturnal reef fishes with and without multibank retinas to evaluate the sensory advantage of having multiple rod layers. We show that fish with multibank retinas have both faster vision and enhanced sensitivity to bright and dim light intensities. Thus, we resolve for the first time the function of multibank retinas - one of the most common visual adaptations in the deep sea. Our findings highlight an unconventional vertebrate visual system as well as the visual capabilities of fishes from the most vast (deep sea) and vibrant (reefs) ecosystems on the planet.

zoology↗

bioRxiv2022

Astrocytic synapse elimination controls ocular dominance plasticity

Ocular dominance plasticity (ODP) is a representative form of experience-dependent synaptic plasticity observed in the primary visual cortex (V1). However, the cellular mechanisms and physiological roles of synapse elimination in ODP are largely unknown. Here, we show that astrocytic phagocytosis of thalamo-cortical synapses in V1 is a critical mediator of ODP. We found that astrocytes, but not microglia, start to engulf thalamo-cortical synapses within 24 hours after monocular deprivation and that astrocytic synapse elimination is highly selective for synapses from the deprived eye, as revealed by AAV1-mediated trans-synaptic anterograde tracing of synapse phagocytosis reporters. Importantly, mice without the Megf10 phagocytic receptor in astrocytes exhibit deficits in eliminating the synapses from the deprived eye, leading to the failure to reduce the number of thalamo-cortical synapses after monocular deprivation. Remarkably, Megf10-deficient animals show severe defects in monocular deprivation-induced cortical synapse remodeling and subsequent expansion of the thalamo-cortical circuitry from the nondeprived eye. Taken together, our data show that astrocytic synapse elimination through MEGF10 is one of the key components in ODP, revealing the physiological importance of astrocytic phagocytosis in experience-dependent synaptic plasticity.

neuroscience↗

bioRxiv2022

Comparative brain structure and the neural network features of cuttlefish and squid

Cuttlefishes, like their octopus cousins, are masters of camouflage by control of body pattern and skin texture to blend in with their surroundings for prey ambush and threat avoidance. Aside from significant progress on the cuttlefish visual perception and communication, a growing number of studies have focused on their behavioural neurobiology and the remarkably rapid and apparently cognitively complex reactions to novel challenges such as spatial learning to solve maze tasks and vertebrate-like cognitive capabilities (e.g. object recognition, number sense and episodic-like memory). Despite intense interest of cuttlefish, much of our knowledge of its neuroanatomy and links to behaviour and ecology comes from one temperate species, the European common cuttlefish, Sepia officinalis. Here we present the first detailed comparison of neuroanatomical features between the tropical cuttlefish and squid and describe differences in basic brain and wiring anatomy using MRI-based techniques and conventional histology. Furthermore, comparisons amongst nocturnal and diurnal cuttlefish species suggest that the characteristic neuroanatomical features infer interspecific variation in visual capabilities, the importance of vision relative to the less utilised chemosensory system and clear links with life modes (e.g. diurnal vs nocturnal), ecological factors (e.g. living depth and ambient light condition) as well as to an extent, phylogeny. These findings link brain heterogeneity to ecological niches and lifestyle, feeding hypotheses around evolutionary history and provide a timely, new technology update to older literature.

neuroscience↗

bioRxiv2021

Lomitapide, a cholesterol-lowering drug, is an anticancer agent that induces autophagic cell death via inhibiting mTOR

Autophagy is a biological process that maintains cellular homeostasis and regulates the internal cellular environment. Hyperactivating autophagy to trigger cell death has been a suggested therapeutic strategy for cancer treatment. Mechanistic target of rapamycin (mTOR) is a crucial protein kinase that regulates autophagy; therefore, using a structure-based virtual screen analysis, we identified lomitapide, a cholesterol-lowering drug, as a potential mTOR complex 1 (mTORC1) inhibitor. Our results showed that lomitapide directly inhibits mTORC1 in vitro and induces autophagy-dependent cancer cell death by decreasing mTOR signaling, thereby inhibiting the downstream events associated with increased LC3 conversion in various cancer cells (e.g., HCT116 colorectal cancer cells) and tumor xenografts. Lomitapide also significantly suppresses the growth and viability along with elevated autophagy in patient-derived colorectal cancer organoids. Furthermore, a combination of lomitapide and immune checkpoint blocking antibodies synergistically inhibits tumor growth in murine MC-38 or B16-F10 pre-clinical syngeneic tumor models. These results elucidates the direct, tumor-relevant immune-potentiating benefits of mTORC1 inhibition by lomitapide, which complement the current immune checkpoint blockade. This study highlights the potential repurposing of lomitapide as a new therapeutic option for cancer treatment.

cancer biology↗

bioRxiv2020

Seeing Nemo: molecular evolution of ultraviolet visual opsins and spectral tuning of photoreceptors in anemonefishes (Amphiprioninae)

Many animals can see ultraviolet (UV) light (shorter than 400 nm) undetectable to human vision. UV vision may have functional importance in many taxa including for foraging and communication in birds, reptiles, insects and teleost fishes. Shallow coral reefs transmit a broad spectrum of light and are rich in UV; driving the evolution of diverse spectral sensitivities in teleost reef fishes, including UV-sensitivity. However, the identities and sites of the specific visual genes that underly vision in reef fishes remain elusive and are useful in determining how molecular evolution has tuned vision to meet the ecological demands of life on the reef. We investigated the visual systems of eleven anemonefish (Amphiprioninae) species, specifically probing for the molecular pathways that facilitate UV-sensitivity. Searching the genomes of anemonefishes, we identified a total of seven functional visual genes from all five vertebrate opsin gene subfamilies. We found rare instances of UV-sensitive SWS1 opsin gene duplications, that produced two functional paralogs (SWS1 and SWS1{beta}) and a pseudogene. We also found separate RH2A opsin gene duplicates not yet reported in the family Pomacentridae. Finally, we report on both qualitative and quantitative aspects of opsin gene expression found in the adult retina of the false clown anemonefish (Amphiprion ocellaris), and their photoreceptor spectral sensitivities measured using microspectrophotometry.

molecular biology↗

bioRxiv2020

CDC50A dependent phosphatidylserine exposure induces inhibitory post-synapse elimination by microglia

Glia contribute to synapse elimination through phagocytosis in the central nervous system. Despite important roles during development and neurological disorders, the "eat-me" signal that initiates glia-mediated phagocytosis of synapses remains largely elusive. Here, by generating inducible conditional knockout mice of Cdc50a, we induced stable exposure of phosphatidylserine in the neuronal outer membrane. Surprisingly, acute Cdc50a deletion in neurons causes specific loss of inhibitory post-synapses without affecting other synapses, thereby generating excessive excitability with appearance of seizure. Ablating microglia or deleting microglial Mertk rescues the loss of inhibitory post-synapses, indicating that microglial phagocytosis is responsible for inhibitory post-synapse elimination. Moreover, inhibitory post-synapses in normal juvenile brains also use phosphatidylserine for synapse pruning by microglia, suggesting that phosphatidylserine may serve as a general "eat-me" signal for inhibitory post-synapse elimination. One Sentence SummaryCdc50a dependent phosphatidylserine exposure functions as an "eat-me" signal for microglia-dependent inhibitory post-synapse elimination

neuroscience↗