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Lieu, S.

Publications and source records attributed to Lieu, S..

2 recordsLinked to original sources

An open-access neuroimaging-compatible virtual town task for assessing human spatial navigation

Spatial navigation is a cognitive skill that draws on multiple processes such as learning, decision-making and memory, which are often updated on a second-by-second timescale. However, many existing virtual paradigms designed to assay spatial navigation cannot target these processes as they unfold or are not designed for integration with concurrent neurophysiological recording. Here, we present and demonstrate our open-access task for neuroimaging: NAturalistic Virtual Assessment of Navigation (NAVAN) combining high-resolution behavioural tracking and integration with electroencephalography. We report data from this task, in which fifty-three participants completed a wayfinding navigation paradigm across twenty-four trials. Navigational efficiency improved significantly following repeated exposure to the environment, although efficiency declined across trials within each block. Self-reported spatial ability (assessed by the Santa Barbara Sense of Direction) predicted performance during early environmental exposure, suggesting concurrent validity. We demonstrated the feasibility of recording electroencephalography during the task, with in-game events streamed and aligned to the neural recording. The task provides researchers with access to detailed behavioural measures and can be adapted by modifying features such as trial number and difficulty. We also provide a step-by-step implementation guide to support reuse and customisation across experimental settings.

neuroscience↗

Exocyst Inactivation in Urothelial Cells Disrupts Autophagy and Activates non-canonical NF-κB

Ureter obstruction is a highly prevalent event during embryonic development and is a major cause of pediatric kidney disease. We have reported that ureteric bud-specific ablation of the exocyst Exoc5 subunit in late-murine gestation results in failure of urothelial stratification, cell death, and complete ureter obstruction. However, the mechanistic connection between disrupted exocyst activity, urothelial cell death, and subsequent ureter obstruction was unclear. Here, we report that inhibited urothelial stratification does not drive cell death during ureter development. Instead, we demonstrate that the exocyst plays a critical role in autophagy in urothelial cells, and that disruption of autophagy activates a urothelial NF-{kappa}B stress response. Impaired autophagy first provokes canonical NF-{kappa}B activity which is progressively followed by increasing non-canonical NF-{kappa}B activity and cell death if the stress remains unresolved. Furthermore, we demonstrate that ureter obstructions can be completely rescued in Exoc5 conditional knockout mice by administering a single dose of pan-caspase inhibitor z-VAD-FMK at E16.5 prior to urothelial cell death. Taken together, ablation of Exoc5 disrupts autophagic stress response and activates progressive NF-{kappa}B signaling which promotes obstructive uropathy.

developmental biology↗