Biology subjects

Lai, C. S. W.

Publications and source records attributed to Lai, C. S. W..

5 recordsLinked to original sources

bioRxiv2026

Closed-loop auditory stimulation during sleep shapes cortical responses and memory consolidation depending on spindle timing

Sleep spindles contribute to memory consolidation, and acoustic stimulation during sleep can modulate spindle activity. However, it remains unclear whether these effects depend on the timing of stimulation relative to the spindle cycle. Using closed-loop spindle detection, we delivered four variants of pink noise either during ongoing spindles or shortly after spindle offset. In Experiment 1, stimulation delivered during a spindle prolonged its duration, whereas stimulation applied shortly after spindle offset, i.e., within the refractory period, delayed the onset of the subsequent spindle. This pattern was consistent across all sound variants, indicating that the stimulation timing, rather than acoustic properties, drove the observed effects. Experiment 2 examined whether post-spindle stimulation influences memory consolidation. Relative to a no-stimulation nap, post-spindle stimulation reduced post-nap deterioration in motor sequence accuracy but did not significantly affect word-pair recall. EEG analyses revealed that stimulation elicited widespread slow oscillation activity without triggering new spindles, demonstrating that cortical processing of external input persists even during the refractory period. Notably, the motor benefit was greatest in participants with lower spindle density during the baseline adaptation nap. Together, these findings challenge the notion that the post-spindle refractory period is a functionally silent interval. Instead, this period remains receptive to external input, capable of eliciting cortical activity and supporting motor memory consolidation even in the absence of new spindle generation.

neuroscience↗

bioRxiv2026

Reactivating conflicting evaluative memories during sleep reduces decision ambivalence

Memory guides everyday evaluations and decision-making. Yet people often encounter inconsistent information about the same target, giving rise to conflicting evaluative memories and decision ambivalence. Decision ambivalence is not only aversive but also reduces confidence, increases hesitation, and leads to maladaptive choices. While sleep consolidates memories, its role in resolving these evaluative conflicts and shaping decision dynamics remains unknown. Here, we investigated how memory reactivation during sleep, a critical period for memory consolidation and transformation, would reconstruct conflicting evaluative memories and thus influence next-day decision ambivalence. In a valence reversal learning procedure, participants first encoded positive or negative cue-outcome associations (A-B) on Day 1, followed by learning A-C associations yet with opposite valences on Day 2 (i.e., Day 1 negative-to-Day 2 positive and Day 1 positive-to-Day 2 negative). During subsequent non-rapid eye movement (NREM) sleep on Day 2 night, half of the cues were re-presented to sleeping participants to reactivate the cue-associated memories. Upon waking up, participants completed post-sleep evaluation and memory tests. Our results showed that cueing reduced decision ambivalence, especially in the negative-to-positive condition, as evidenced by less curved mouse-tracking trajectories. Meanwhile, cueing promoted the integration of conflicting evaluative memories, again in the negative-to-positive condition. Critically, cueing-induced ambivalence reduction was evident only for items that were integrated after sleep. Electrophysiologically, stronger cue-elicited delta power during NREM sleep predicted next-day ambivalence reduction, while higher cue-elicited spindle probabilities were associated with better memory integration. Together, our findings suggest that memory reactivation during post-learning NREM sleep actively reorganizes conflicting memories, providing a mechanistic pathway through which offline memory reprocessing resolves waking decision ambivalence.

neuroscience↗

bioRxiv2026

NORAD orchestrates KLC1-mediated SFPQ transport via liquid-liquid phase separation

Neuronal function requires precise long-distance axonal transport mediated by molecular motors and RNA-binding proteins like SFPQ, though regulatory mechanisms remain poorly defined. We identify long non-coding RNA NORAD as a master regulator of this process through liquid-liquid phase separation (LLPS). While SFPQ and kinesin-1 mediate cargo delivery, the specific RNA coordinating their interaction was unknown. We demonstrate NORAD directly binds kinesin light chain 1 (KLC1) and promotes SFPQ condensation into dynamic LLPS droplets, enabling efficient transport. CRISPR-assisted mapping and functional assays show NORAD depletion disrupts granule dynamics, impairs neuroprotective mRNA localization, and induces axonal degeneration. In vitro reconstitution confirms NORAD-KLC1 synergy enhances SFPQ phase separation, and neuron-specific knockout mice exhibit motor deficits with reduced neuronal density. These findings establish the first evidence of lncRNA NORAD-mediated LLPS in axonal transport, revealing a new paradigm for RNA-guided neuronal maintenance.

molecular biology↗

bioRxiv2023

The Effect of Transcranial Direct Current and Magnetic Stimulation on Fear Extinction and Return of Fear: A meta-analysis and Systematic Review

Anxiety and fear-related disorders are among the most prevalent mental illnesses. Non-invasive brain stimulation methods such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) have been employed to modulate anxiety and fear-related symptoms, but their therapeutic effects remain inconclusive. Pavlovian conditioning and extinction are experimental analogues of exposure therapy that investigate the neural mechanisms of fear extinction and return of fear. We conducted a meta-analysis and qualitative review on the effects of tDCS and TMS on fear extinction and return of fear in non-primate animals and humans. Results show that both anodal and cathodal tDCS over the prefrontal cortex inhibit short-term contextual and cued fear retrieval in animal models. In human studies, anodal tDCS over the medial/ventromedial prefrontal cortex enhances fear extinction, whereas TMS over the dorsolateral/ventromedial prefrontal cortex inhibits return of fear. Our findings suggest the optimal non-invasive brain stimulation protocols for threat extinction in humans.

neuroscience↗

bioRxiv2022

Tomographic-encoded multiphoton (TEMP) microscopy

Axial scanning in multiphoton microscopy (MPM) is typically realized by mechanically shifting either the objective or the sample. However, the scan speed is usually hindered by the mechanical inertia of the bulky mass. Although the extended depth of field provided by the non-diffracting beam allows fast volumetric imaging, it abandons the axial resolution. Here, we demonstrate a novel and powerful tomographic technique using the Bessel droplet in MPM, termed Tomographic-Encoded MultiPhoton (TEMP) microscopy. We show that benefiting from the high-order nonlinear excitation in MPM, the side-lobes cancellation and smaller beam focus of the Bessel droplet realize better image quality. The TEMP microscopy allows fast axial scanning, less risks of photodamage and photobleaching, and high-resolution and high-contrast imaging. Furthermore, fewer raw images are required for the 3D image reconstruction. To demonstrate its usability and advantages for scattering tissues and biomedical applications, we showcase the TEMP microscopy with highly scattering fluorescence microspheres and mouse brain slice. More details can be visualized by the Bessel droplet compared with the conventional Gaussian and Bessel beam. More importantly, the TEMP technique is an easy-plug-in method for the current microscopy system. The TEMP microscopy is promising for fast volumetric multiphoton imaging, especially for highly scattering tissues.

bioengineering↗