Biology subjects

Leng, X.

Publications and source records attributed to Leng, X..

24 records · Page 2Linked to original sources

bioRxiv2020

Dissociable influences of reward and punishment on adaptive cognitive control

To invest effort into any cognitive task, people must be sufficiently motivated. Whereas prior research has focused primarily on how the cognitive control required to complete these tasks is motivated by the potential rewards for success, it is also known that control investment can be equally motivated by the potential negative consequence for failure. Previous theoretical and experimental work has yet to examine how positive and negative incentives differentially influence the manner and intensity with which people allocate control. Here, we develop and test a normative model of control allocation under conditions of varying positive and negative performance incentives. Our model predicts, and our empirical findings confirm, that rewards for success and punishment for failure should differentially influence adjustments to the evidence accumulation rate versus response threshold, respectively. This dissociation further enabled us to infer how motivated a given person was by the consequences of success versus failure. Author SummaryFrom the school to the workplace, whether someone achieves their goals is determined largely by the mental effort they invest in their tasks. Recent work has demonstrated both why and how people adjust the amount of effort they invest in response to variability in the rewards expected for achieving that goal. However, in the real world, we are motivated both by the positive outcomes our efforts can achieve (e.g., praise) and the negative outcomes they can avoid (e.g., rejection), and these two types of incentives can motivate adjustments not only in the amount of effort we invest but also the types of effort we invest (e.g., whether to prioritize performing the task efficiently or cautiously). Using a combination of computational modeling and a novel task that measures voluntary effort allocation under varying incentive conditions, we show that people should and do engage dissociable forms of mental effort in response to positive versus negative incentives. With increasing rewards for achieving their goal, they prioritize efficient performance, whereas with increasing penalties for failure they prioritize performing cautious performance. We further show that these dissociable strategies enable us to infer how motivated a given person was based on the positive consequences of success relative to the negative consequences of failure.

neuroscience↗

bioRxiv2020

A neurogenetic mechanism of experience-dependent suppression of aggression

Aggression is an ethologically important social behavior1 but excessive aggression can be detrimental to animal fitness2,3. Social experiences among conspecific individuals reduce aggression in a wide range of animals4. However, the genetic and neural basis for the experience-dependent suppression of aggression remains largely unknown. Here we found that nervy (nvy), a Drosophila homolog of vertebrate myeloid translocation gene (MTG)5 involved in transcriptional regulation6-8, suppresses aggression via its action in a specific subset of neurons. Loss-of-function mutation of the nvy gene resulted in hyper-aggressiveness only in socially experienced flies, whereas overexpression of nvy suppressed spontaneous aggression in socially naive flies. The loss-of-function nvy mutant exhibited persistent aggression under various contexts in which wild-type flies transition to escape or courtship behaviors. Knockdown of nvy in octopaminergic/tyraminergic (OA/TA) neurons increased aggression, phenocopying the nvy mutation. We found that a subpopulation of OA/TA cells specifically labeled by nvy is required for the social-experience-dependent suppression of aggression. Moreover, cell-type-specific transcriptomics on nvy-expressing OA/TA neurons revealed aggression-controlling genes that are likely downstream of nvy. Our results are the first to describe the presence of a specific neuronal subpopulation in the central brain that actively suppresses aggression in a social-experience-dependent manner, illuminating the underlying genetic mechanism.

neuroscience↗

bioRxiv2020

Quantitative comparison of Drosophila behavior annotations by human observers and a machine learning algorithm

Automated quantification of behavior is increasingly prevalent in neuroscience research. Human judgments can influence machine-learning-based behavior classification at multiple steps in the process, for both supervised and unsupervised approaches. Such steps include the design of the algorithm for machine learning, the methods used for animal tracking, the choice of training images, and the benchmarking of classification outcomes. However, how these design choices contribute to the interpretation of automated behavioral classifications has not been extensively characterized. Here, we quantify the effects of experimenter choices on the outputs of automated classifiers of Drosophila social behaviors. Drosophila behaviors contain a considerable degree of variability, which was reflected in the confidence levels associated with both human and computer classifications. We found that a diversity of sex combinations and tracking features was important for robust performance of the automated classifiers. In particular, features concerning the relative position of flies contained useful information for training a machine-learning algorithm. These observations shed light on the importance of human influence on tracking algorithms, the selection of training images, and the quality of annotated sample images used to benchmark the performance of a classifier (the ‘ground truth’). Evaluation of these factors is necessary for researchers to accurately interpret behavioral data quantified by a machine-learning algorithm and to further improve automated classifications.Significance Statement Accurate quantification of animal behaviors is fundamental to neuroscience. Here, we quantitatively assess how human choices influence the performance of automated classifiers trained by a machine-learning algorithm. We found that human decisions about the computational tracking method, the training images, and the images used for performance evaluation impact both the classifier outputs and how human observers interpret the results. These factors are sometimes overlooked but are critical, especially because animal behavior is itself inherently variable. Automated quantification of animal behavior is becoming increasingly prevalent: our results provide a model for bridging the gap between traditional human annotations and computer-based annotations. Systematic assessment of human choices is important for developing behavior classifiers that perform robustly in a variety of experimental conditions.Competing Interest StatementThe authors have declared no competing interest.View Full Text

animal behavior and cognition↗

bioRxiv2018

Bacteroides fragilis defense against Cronobacter sakazakii -induced pathogenicity by regulating the intestinal epithelial barrier function and attenuating both apoptotic and pyroptotic cell death

Cronobacter sakazakii (CS), an important pathogen, is associated with the development of necrotizing enterocolitis (NEC), infant sepsis, and meningitis. Several randomized prospective clinical trials demonstrated that oral probiotics could decrease the incidence of NEC. Previously, we isolated and characterized a novel probiotic, B. fragilis strain ZY-312. However, it remains unclear how ZY-312 protects the host from the effects of CS infection. To understand the underlying mechanisms triggering the probiotic effects, we tested the hypothesis that there was a cross-talk between probiotics/probiotics-modulated microbiota and the local immune system, governed by the permeability of the intestinal mucosa using in vitro and in vivo models for the intestinal permeability. The probiotic effects of ZY-312 on intestinal epithelial cells were first examined, which revealed that ZY-312 inhibited CS invasion, CS-induced dual cell death (pyroptosis and apoptosis), and epithelial barrier dysfunction in vitro and in vivo. ZY-312 also decreased the expression of an inflammasome (NOD-like receptor family member pyrin domain-containing protein 3 (NLRP3), caspase-3, and serine protease caspase-1 in a neonatal rat model. Furthermore, ZY-312 significantly modulated the compositions of the intestinal bacterial communities, and decreased the relative abundances of Proteobacteria, Gamma proteobacteria, but increased the relative abundance of Bacteroides and Bacillus in neonatal rats. In conclusion, our findings have shown for the first time that the probiotic, B. fragilis ZY-312, suppresses CS-induced NEC by modulating the pro-inflammatory response and dual cell death (apoptosis and pyroptosis).\n\nAuthor summaryCronobacter sakazakii, a major necrotizing enterocolitis pathogen, is used as a model microorganism for the study of opportunistic bacteria in the pathogenesis of necrotizing enterocolitis. Here, we have now unequivocally demonstrated that both apoptotic and pyroptotic stimuli contribute to the pathogenesis of Cronobacter sakazakii -induced necrotizing enterocolitis. Previously, we isolated and characterized a novel probiotic, B. fragilis strain ZY-312. We found that the ZY-312 defense against Cronobacter sakazakii-induced necrotizing enterocolitis by inhibiting Cronobacter sakazakii invasion, epithelial barrier dysfunction, the expression of inflammatory cytokines and dual cell death (pyroptosis and apoptosis). This study demonstrates the utility of ZY-312 as a promising probiotic agent for the prevention and treatment of various intestinal diseases, including NEC.

microbiology↗

bioRxiv2018

A conserved glycine harboring disease-associated mutations is required for slow deactivation and high Ca2+ permeability in NMDA receptors

A variety of de novo and inherited missense mutations associated with neurological disorders are found in the NMDA receptor M4 transmembrane helices, which are peripheral to the pore domain in eukaryotic ionotropic glutamate receptors. Subsets of these mutations affect receptor gating with dramatic effects, including in one instance halting it, occurring at a conserved glycine near the extracellular end of M4. Functional experiments and molecular dynamic simulations of constructs with and without substitutions at this glycine indicate that it acts as a hinge, permitting the intracellular portion of the ion channel to laterally expand. This expansion stabilizes long-lived open states leading to slow deactivation and high Ca2+ permeability. Our studies provide a functional and structural framework for the effect of missense mutations on NMDARs at central synapses and highlight how the M4 segment may represent a pathway for intracellular modulation of NMDA receptor function.

neuroscience↗

bioRxiv2018

Transcription-driven Chromatin Repression of Intragenic Promoters

Progression of RNA polymerase II (RNAPII) transcription relies on the appropriately positioned activities of elongation factors. The resulting profile of factors and chromatin signatures along transcription units provides a \"positional information system\" for transcribing RNAPII. Here, we investigate a chromatin-based mechanism that suppresses intragenic initiation of RNAPII transcription. We demonstrate that RNAPII transcription across gene promoters represses their function in plants. This repression is characterized by reduced promoter-specific molecular signatures and increased molecular signatures associated with RNAPII elongation. The FACT histone chaperone complex is required for this repression mechanism. Genome-wide mapping of Transcription Start Sites (TSSs) reveals thousands of discrete intragenic TSS positions in FACT mutants. Histone 3 lysine 4 mono-methylation poises exonic sites to initiate RNAPII transcription in FACT mutants. Uncovering the mechanism for intragenic TSS repression through the act of RNAPII elongation has important implications for understanding pervasive RNAPII transcription and the regulation of transcript isoform diversity.

genomics↗