Biology subjects

Li, S.-J.

Publications and source records attributed to Li, S.-J..

3 recordsLinked to original sources

bioRxiv2024

A disinhibitory basal forebrain to cortex projection supports sustained attention

Sustained attention, as an essential cognitive faculty governing selective sensory processing, exhibits remarkable temporal fluctuations. However, the underlying neural circuits and computational mechanisms driving moment-to-moment attention fluctuations remain elusive. Here we demonstrate that cortex-projecting basal forebrain parvalbumin-expressing inhibitory neurons (BF-PV) mediate sustained attention in mice performing an attention task. BF-PV activity predicts the fluctuations of attentional performance metrics [-] reaction time and accuracy [-] trial-by-trial, and optogenetic activation of these neurons enhances performance. BF-PV neurons also respond to motivationally salient events, such as predictive cues, rewards, punishments, and surprises, which a computational model explains as representing motivational salience for allocating attention over time. Furthermore, we found that BF-PV neurons produce cortical disinhibition by inhibiting cortical PV+ inhibitory neurons, potentially underpinning the observed attentional gain modulation in the cortex. These findings reveal a disinhibitory BF-to-cortex projection that regulates cortical gain based on motivational salience, thereby promoting sustained attention. HIGHLIGHTSO_LIBF-PV activity predicts attentional performance metrics: reaction time and accuracy C_LIO_LIBF-PV responses reflect the computation of motivational salience-guided attention allocation C_LIO_LIOptogenetic activation of BF-PV neurons improves attentional performance C_LIO_LIBF-PV neurons produce cortical disinhibition through topographic projections and mediate gain modulation C_LI

neuroscience↗

bioRxiv2022

Hydroxycitric acid inhibits oxalate nephropathies formation through crystallization regulation and activation of the PPARα pathway

Oxalate-induced nephropathies comprise a range of kidney disorders, for which there are no efficient pharmacological treatments. Hydroxycitric acid (HCA) is a derivative of citric acid with a variety of pharmacological activities including reducing body weight and calcium salt deposition. However, the specific mechanism of inhibition of oxalate nephropathies by this compound is not well understood. In this study, we successfully applied bioinformatics-based and simulated drug molecular docking approaches to predict potential targets of HCA. Subsequently, we explored the molecular mechanisms of HCA inhibition of renal calcium oxalate (CaOx) deposition and nephrotoxicity in an oxalate-induced NRK-52E cell model and an oxalate nephropathy rat model. HCA could effectively inhibit CaOx crystal deposition and reduce crystal adhesion and oxidative damage, effectively inhibit lipid deposition caused by high oxalate, and reduce lipid nephrotoxicity. HCA is more effective than traditional stone medications in inhibiting CaOx deposition and kidney damage. Further cellular transcriptomic analysis and in vitro results showed that HCA could stably bind peroxisome proliferator-activated receptor (PPAR) and promote PPAR-RXR heterodimer formation, thus promoting the expression of downstream oxidative stress molecules (Nrf2, HO-1, SOD) and inhibiting calcium ion release and mitochondrial dysfunction, thus reducing oxalate-induced renal lipid peroxidation damage. Therefore, HCA, a novel drug with the ability to modulate lipid metabolism and inhibit CaOx formation, may be a therapeutic option for the treatment of oxalate nephropathies.

biochemistry↗

bioRxiv2019

EphB6 regulates social behavior through gut microbiota-mediated vitamin B6 metabolism and excitation/inhibition balance of medial prefrontal cortex in mice

Autism spectrum disorder (ASD) is a developmental disorder with no effective pharmacological treatments so far. Gut microbiota has been suggested to contribute to autistic symptoms. However, the key genes and the mechanisms linking gut microbiota and brain dysfunctions in ASD are still unclear. Here, we found deletion of EphB6, an ASD-associated candidate gene, induced dysregulated gut microbiota and autism-like behavior in mice. More importantly, transplanting fecal microbiota from EphB6-deficient mice resulted in disturbed gut microbiota and autism-like behavior in antibiotics-treated C57BL/6J mice. Meanwhile, transplanting fecal microbiota from wild-type mice ameliorated disturbed gut microbiota and autism-like behavior in mice with deletion of EphB6. At the metabolic levels, dysregulated gut microbiota led to vitamin B6 and dopamine defects in EphB6-deficient mice. At the cellular levels, excitation/inhibition (E/I) imbalance in medial prefrontal cortex was induced by gut microbiota-mediated defects of vitamin B6 metabolism in EphB6-deficient mice. Our study uncovers a key role for EphB6 in regulation of social behavior by gut microbiota-mediated vitamin B6 metabolism, dopamine synthesis and E/I balance, suggesting a new strategy for treatment of ASD patients.

neuroscience↗