Biology subjects

Qi, X.-L.

Publications and source records attributed to Qi, X.-L..

5 recordsLinked to original sources

bioRxiv2025

Chemerin-CMKLR1 mediated OGD/R induced Mitochondrial Dysfunction, Oxidative Stress, and Autophagy differentially in Microglia and Neurons

IntroductionIschemia-reperfusion (I/R) injury exacerbates tissue damage upon reperfusion after ischemia. The impact of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1) on I/R injury remains poorly understood. We hypothesized that chemerin-CMKLR1 differentially regulates signaling in microglia and neuronal cells oxygen-glucose deprivation/reoxygenation (OGD/R), influencing mitochondrial function, oxidative stress, and autophagy. MethodsUsing BV2 microglia and Neuro-2a (N2a) neuronal cells, we examined OGD/R-induced changes in autophagy associated proteins, chemerin and CMKLR1 expression. We investigated the functional consequences of CMKLR1 overexpression and chemerin treatment on oxidative stress, apoptosis, autophagy, and mitochondrial dynamics in BV2 microglia and N2a neuronal cells. ResultsOGD/R downregulated CMKLR1 while upregulating autophagy in both BV2 microglia and N2a cells; While chemerin expression decreased in BV2 microglia but increased in N2a cells following OGD/R. Treatment with chemerin dose-dependently reduced oxidative stress and apoptosis while enhancing mitochondrial fusion, suppressing fission, and promoting autophagy and mitochondrial function in both cell types under OGD/R. CMKLR1 overexpression exacerbated mitochondrial respiratory dysfunction, mitochondrial fusion, fission, and elevated autophagy (LC3II/LC3I and Pink1 levels), with cell-type-specific differences observed in Parkin and P62 regulation. ConclusionOur study demonstrates cell-type-specific regulation of chemerin-CMKLR1 signaling in I/R injury, and distinct mitophagy activation mechanisms in microglia and neurons. These findings suggest cell-type specific modulation of chemerin-CMKLR1 as a potential therapeutic target in preserving mitochondrial homeostasis, modulating autophagy, mitophagy and reducing oxidative stress, apoptosis in both microglia and neurons for mitigating I/R injury.

neuroscience↗

bioRxiv2024

Brain structure and activity predicting cognitive maturation in adolescence

Cognitive abilities of primates, including humans, continue to improve through adolescence 1,2. While a range of changes in brain structure and connectivity have been documented 3,4, how they affect neuronal activity that ultimately determines performance of cognitive functions remains unknown. Here, we conducted a multilevel longitudinal study of monkey adolescent neurocognitive development. The developmental trajectory of neural activity in the prefrontal cortex accounted remarkably well for working memory improvements. While complex aspects of activity changed progressively during adolescence, such as the rotation of stimulus representation in multidimensional neuronal space, which has been implicated in cognitive flexibility, even simpler attributes, such as the baseline firing rate in the period preceding a stimulus appearance had predictive power over behavior. Unexpectedly, decreases in brain volume and thickness, which are widely thought to underlie cognitive changes in humans 5 did not predict well the trajectory of neural activity or cognitive performance changes. Whole brain cortical volume in particular, exhibited an increase and reached a local maximum in late adolescence, at a time of rapid behavioral improvement. Maturation of long-distance white matter tracts linking the frontal lobe with areas of the association cortex and subcortical regions best predicted changes in neuronal activity and behavior. Our results provide evidence that optimization of neural activity depending on widely distributed circuitry effects cognitive development in adolescence.

neuroscience↗

bioRxiv2023

Training-dependent gradients of timescales of neural dynamics in the primate prefrontal cortex and their contributions to working memory

Cortical neurons exhibit multiple timescales related to dynamics of spontaneous fluctuations (intrinsic timescales) and response to task events (seasonal timescales) in addition to selectivity to task-relevant signals. These timescales increase systematically across the cortical hierarchy, e.g., from parietal to prefrontal and cingulate cortex, pointing to their role in cortical computations. It is currently unknown whether these timescales depend on training in a specific task and/or are an inherent property of neurons, and whether more fine-grained hierarchies of timescales exist within specific cortical regions. To address these questions, we analyzed single-cell recordings within five subregions of the prefrontal cortex (PFC) of male macaques before and after training on a working-memory task. We found fine-grained but opposite gradients of intrinsic and seasonal timescales that mainly appeared after training. Intrinsic timescales decreased whereas seasonal timescales increased from posterior to anterior subregions within both dorsal and ventral PFC. Moreover, training was accompanied by increases in proportions of neurons that exhibited intrinsic and seasonal timescales. These effects were comparable to the emergence of response selectivity due to training. Finally, task selectivity accompanied opposite neural dynamics such that neurons with task-relevant selectivity exhibited longer intrinsic and shorter seasonal timescales. Notably, neurons with longer intrinsic and shorter seasonal timescales exhibited superior population-level coding, but these advantages extended to the delay period mainly after training. Together, our results provide evidence for plastic, fine-grained gradients of timescales within PFC that can influence both single-cell and population coding, pointing to the importance of these timescales in understanding cognition. Significance statementRecent studies have demonstrated that neural responses exhibit dynamics with different timescales that follow a certain order or hierarchy across cortical areas. While the hierarchy of timescales is consistent across different tasks, it is unknown if these timescales emerge only after training or if they represent inherent properties of neurons. To answer this question, we estimated multiple timescales in neural response across five subregions of the monkeys lateral prefrontal cortex before and after training on a working-memory task. Our results provide evidence for fine-grained gradients related to certain neural dynamics. Moreover, we show that these timescales depend on and can be modulated by training in a cognitive task, and contribute to encoding of task-relevant information at single-cell and population levels.

neuroscience↗

bioRxiv2020

Emergence of Non-Linear Mixed Selectivity in Prefrontal Cortex after Training

Neurons in the prefrontal cortex (PFC) are typically activated by different cognitive tasks, and also by different stimuli and abstract variables within these tasks. A single neurons selectivity for a given stimulus dimension often changes depending on its context, a phenomenon known as nonlinear mixed selectivity (NMS). It has previously been hypothesized that NMS emerges as a result of training to perform tasks in different contexts. We tested this hypothesis directly by examining the neuronal responses of different PFC areas before and after monkeys were trained to perform different working memory tasks involving visual stimulus locations and/or shapes. We found that training induces a modest increase in the proportion of PFC neurons with NMS exclusively for spatial working memory, but not shape working memory tasks, with area 9/46 undergoing the most significant increase in NMS cell proportion. We also found that increased working memory task complexity, in the form of simultaneously storing location and shape combinations, does not increase the degree of NMS for stimulus shape with other task variables. Lastly, in contrast to the previous studies, we did not find evidence that NMS is predictive of task performance. Our results thus provide critical insights on the representation of stimuli and task information in neuronal populations, which may pave the way to a greater understanding of neural selectivity in working memory. SIGNIFICANCE STATEMENTHow multiple types of information are represented in working memory remains a complex computational problem. It has been hypothesized that nonlinear mixed selectivity allows neurons to efficiently encode multiple stimuli in different contexts, after subjects have been trained in complex tasks. Our analysis of prefrontal recordings obtained before and after training monkeys to perform working memory tasks only partially agreed with this prediction, in that nonlinear mixed selectivity emerged for spatial but not shape information, and mostly in mid-dorsal PFC. Nonlinear mixed selectivity also displayed little modulation across either task complexity or correct performance. These results point to other mechanisms, in addition to nonlinear mixed selectivity, to represent complex information about stimulus and context in neuronal activity.

neuroscience↗

bioRxiv2019

Nucleus Basalis Stimulation Stabilizes Attractor Networks and Enhances Task Representation in Prefrontal Cortex

Acetylcholine in the neocortex is critical for executive function. Degeneration of the basal forebrain cholinergic system is associated with cognitive decline in aging and Alzheimers disease. Cholinergic agonists and acetylcholinesterase inhibitors improve cognitive performance as does intermittent electrical stimulation of the cortical source of acetylcholine, the Nucleus Basalis (NB) of Meynert. Here we tested how NB stimulation improves working memory behavior and alters its neural code. NB stimulation increased dorsolateral prefrontal activity during the delay period of working memory tasks but did not strengthen phasic responses to the optimal visual stimulus of each neuron. Unexpectedly, improvement of behavioral performance was not the result of increased neural selectivity. Tuning of neuronal responses broadened, which rendered an attractor network more stable and filtered distracting visual stimuli more effectively. Thus, the effects of acetylcholine on prefrontal neural activity and selectivity in working memory contrast those of dopamine and stabilize neural ensembles based on neuromodulatory tone.

neuroscience↗