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Biology subjects

Wu, Y.-F.

Publications and source records attributed to Wu, Y.-F..

3 recordsLinked to original sources

Active Escape or Active Change? Decomposing Pavlovian Bias into Non-emotional Components

Pavlovian bias, a motor bias driven by emotionally-valenced context, has long been considered a proxy for emotion-action processing, which may become aberrant in affective disorders and suicidality. The orthogonal valenced Go/NoGo paradigm was developed to isolate this bias and has been widely adopted in translational psychiatry research under this interpretation. However, several unresolved theoretical inconsistencies highlight the need to dissociate potential confounding factors within this paradigm before assigning mechanistic and clinical interpretations to its findings. Using a novel paradigm that fully orthogonalized valence, action, and aimed transition in a normative sample of 25 individuals, we found that the "active escape bias" previously observed in aversive contexts--and interpreted as reflecting suicidality in the clinical population--was reproduced in appetitive contexts using trials with the same transition structure. Furthermore, computational modeling indicated that the bias patterns isolated by the orthogonal paradigm are primarily explained by the combined effects of aimed transition and cue salience, without requiring emotional-valence modulation. These findings call for a fundamental reconsideration of how orthogonal Go/NoGo paradigms are interpreted in translational psychiatry, particularly how the behavior they isolate is mechanistically linked to affective symptoms.

neuroscience↗

High-resolution volumetric intravital imaging reveals asymmetric serotonin-dependent post-shock activity in the Drosophila brain

Volumetric intravital imaging of adult Drosophila brains remains challenging due to optical scattering and speed limitations of conventional microscopy. Here, we present V-shape Bessel-beam light-sheet microscopy (vSPIM), an upright, high-speed platform achieving subcellular resolution across large, opaque volumes in vivo. Through real-time calcium imaging in adult Drosophila, vSPIM uncovered two unprecedented phenomena: first, a complex ensemble of approximately 150 olfactory projection neuron boutons (more than 400 per hemisphere) resolved 18 distinct odor valence coding patterns within the dense mushroom body calyx, aligning with connectomic architecture. Second, vSPIM revealed a previously uncharacterized asymmetric, serotonin-dependent post-shock firing (PsF) response. This PsF activity emerged within the mushroom body and dopaminergic neurons only after repetitive aversive stimulation, distinct from canonical dopamine-driven reinforcement signals. Finally, we demonstrated the versatility of vSPIM by tracking corneal endothelial dynamics during mouse wound healing. Overall, vSPIM establishes a scalable framework for intravital imaging, bridging the gap between optical innovation and circuit physiology in adult tissues.

neuroscience↗

Expansion microscopy for super-resolution imaging of collagen-abundant tissues

Expansion microscopy (ExM) is popular for three-dimensional ultrastructural imaging of cultured cells and tissue slices at nanoscale resolution with conventional microscopes via physical expansion of biological tissues. However, the application of this technology to collagen-abundant thick tissues is challenging. We demonstrate a new method, collagen expansion microscopy (ColExM), optimized for expanding tissues containing more than 70% collagen. ColExM succeeded in 4.5-fold linear expansion with minimal structural distortion of corneal and skin tissues. It was also compatible with immunostaining, allowing super-resolution visualization of three-dimensional neural structures innervating hair follicles and corneas. With ColExM, we succeeded in identifying individual mitochondria and previously unrecognized dendritic spine-like structures of corneal nerves. ColExM also enabled fine mapping of structural rearrangement of tight junctions and actin cytoskeletons. Therefore, this method can facilitate the exploration of three-dimensional nanoscale structures in collagen-rich tissues.

bioengineering↗