Biology subjects

Lee, I.-C.

Publications and source records attributed to Lee, I.-C..

5 recordsLinked to original sources

bioRxiv2026

Engineering a performance-improved, axon-targeted kalium channelrhodopsin for optogenetic neuropathway inhibition

Optogenetic neuropathway inhibition is a powerful approach for dissecting circuit functions. This strategy, however, frequently encounters practical challenges due to insufficient expression or performance of the optogenetic silencer on axonal projections/terminals. HcKCR1, a light-gated potassium-selective channel from Hyphochytrium catenoides, has shown great promise for optogenetic inhibition. Unfortunately, the application of HcKCR1 in neuropathway manipulations is hindered by its unsatisfactory gating properties and poor axonal trafficking. To overcome these hurdles, we first engineered a performance-improved HcKCR1 (piKCR) that allowed more reliable neuronal inhibition at low intensities of green or red light. We next engineered an axon-targeted piKCR (piKCR.AT) that demonstrated long-range axonal trafficking and optical presynaptic inhibition in the mouse hippocampus. When piKCR.AT was expressed in the cerebellar Purkinje Cells (PCs), optical manipulation of PC outputs to the deep cerebellar nuclei robustly disrupted mouse movement on the balance beam. With enhanced performance and axonal distribution, piKCR.AT may provide new opportunities for elucidating neuropathway functions in health and diseases.

bioengineering↗

bioRxiv2022

Ocular tropism of SARS-CoV-2 with retinal inflammation through neuronal invasion in animal models

Although ocular manifestations are commonly reported in patients with coronavirus disease 2019 (COVID-19), there is currently no consensus on ocular tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To investigate this, we infected K18-hACE2 mice with SARS-CoV-2 using various routes. We observed ocular manifestation and retinal inflammation with cytokine production in the eyes of intranasally (IN) infected mice. An intratracheal (IT) injection resulted in virus spread from the lungs to the brain and eyes via trigeminal and optic nerves. Ocular and neuronal invasion were confirmed by an intracerebral (IC) infection. Notably, eye-dropped (ED) virus did not infect the lungs and was undetectable with time. Using infectious SARS-CoV-2-mCherry clones, we demonstrated the ocular and neurotropic distribution of the virus in vivo by a fluorescence-imaging system. Evidence for the ocular tropic and neuroinvasive characteristics of SARS-CoV-2 was confirmed in wild-type Syrian hamsters. Our data provides further understanding of the viral transmission; SARS-CoV-2 clinical characteristics; and COVID-19 control procedures. SummarySARS-CoV-2 can spread from the respiratory tract to the brain and eyes via trigeminal and optic nerves in animal models. This ocular tropism of SARS-CoV-2 through neuronal invasion likely causes ocular manifestation and retinal inflammation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/488607v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@151c2d5org.highwire.dtl.DTLVardef@ce3aeforg.highwire.dtl.DTLVardef@17f453aorg.highwire.dtl.DTLVardef@99e9c2_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2020

External light dark cycle shapes gut microbiota through intrinsically photosensitive retinal ganglion cells

Gut microbiota has been shown to involve in many physiological functions such as metabolism, brain development, and neuron degeneration disease. Intriguingly, many microbes in the digestive tract do not maintain a constant level of their relative abundance but show daily oscillations under normal conditions. Recent evidence indicates that chronic jetlag, constant darkness, or deletion of the circadian core gene can alter the composition of gut microbiota and dampen the daily oscillation of gut microbes. These studies suggest that the interaction between the host circadian clock and the light-dark cycle plays an important role in gut homeostasis and microbiota. However, how or whether environmental factors such as the light-dark cycle could modulate gut microbiota is still poorly understood. Using genetic mouse models and 16s rRNA metagenomic analysis, we found that light-dark cycle information transmitted by the ipRGC-sympathetic circuit was essential for daily oscillations of gut microbes under temporal restricted high fat diet condition. Furthermore, aberrant light exposure such as dim light at night (dLAN), acting through intrinsically photosensitive retinal ganglion cells (ipRGCs), could alter the composition, relative abundance, and daily oscillations of gut microbiota. Together, our results indicate that external stimulation, such as light-dark cycle information, through the sensory system can modulate gut microbiota in the direction from the brain to the gut.

neuroscience↗

bioRxiv2020

Visual effort moderates postural cascade dynamics

Standing still and focusing on a visible target in front of us is a preamble to many coordinated behaviors (e.g., reaching an object). Hiding behind its apparent simplicity is a deep layering of texture at many scales. The task of standing still laces together activities at multiple scales: from ensuring that a few photoreceptors on the retina cover the target in the visual field on an extremely fine scale to synergies spanning the limbs and joints at smaller scales to the mechanical layout of the ground underfoot and optic flow in the visual field on the coarser scales. Here, we used multiscale probability density function (PDF) analysis to show that postural fluctuations exhibit similar statistical signatures of cascade dynamics as found in fluid flow. In participants asked to stand quietly, the oculomotor strain of visually fixating at different distances moderated postural cascade dynamics. Visually fixating at a comfortable viewing distance elicited posture with a similar cascade dynamics as posture with eyes closed. Greater viewing distances known to stabilize posture showed more diminished cascade dynamics. In contrast, nearest and farthest viewing distances requiring greater oculomotor strain to focus on targets elicited a dramatic strengthening of postural cascade dynamics, reflecting active postural adjustments. Critically, these findings suggest that vision stabilizes posture by reconfiguring the prestressed poise that prepares the body to interact with different spatial layouts.

neuroscience↗

bioRxiv2020

Visual effort moderates a self-correcting nonlinear postural control policy

Visually guided postural control emerges in response to task constraints. Task constraints generate physiological fluctuations that foster the exploration of available sensory information at many scales. Temporally correlated fluctuations quantified using fractal and multifractal metrics have been shown to carry perceptual information across the body. The risk of temporally correlated fluctuations is that stable sway appears to depend on a healthy balance of standard deviation (SD): too much or too little SD entails destabilization of posture. This study presses on the visual guidance of posture by prompting participants to quietly stand and fixate at distances within, less than, and beyond comfortable viewing distance. Manipulations of the visual precision demands associated with fixating nearer and farther than comfortable viewing distance reveals an adaptive relationship between SD and temporal correlations in postural fluctuations. Changing the viewing distance of the fixation target shows that increases in temporal correlations and SD predict subsequent reductions in each other. These findings indicate that the balance of SD within stable bounds may depend on a tendency for temporal correlations to self-correct across time. Notably, these relationships became stronger with greater distance from the most comfortable viewing and reaching distance, suggesting that this self-correcting relationship allows the visual layout to press the postural system into a poise for engaging with objects and events. Incorporating multifractal analysis showed that all effects attributable to monofractal evidence were better attributed to multifractal evidence of nonlinear interactions across scales. These results offer a glimpse of how current nonlinear dynamical models of self-correction may play out in biological goal-oriented behavior. We interpret these findings as part of the growing evidence that multifractal nonlinearity is a modeling strategy that resonates strongly with ecological-psychological approaches to perception and action.

neuroscience↗