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Qi, K.

Publications and source records attributed to Qi, K..

9 recordsLinked to original sources

Motor Cortical Computations Underlying Natural Dexterous Movement in Freely Flying Bats

Elucidating the neural computations underlying natural, complex movement remains a fundamental challenge in neuroscience. Bat flight presents a formidable motor control challenge, requiring the use of hand-like wings whose many degrees of freedom must be precisely coordinated to enable rapid three-dimensional maneuvers. Here we performed large-scale wireless recordings of neuronal ensembles from the wing motor cortex of freely flying bats using Neuropixels probes, alongside detailed 3D pose tracking of wing kinematics. Despite the complexity of flight control, bats repeatedly executed highly accurate flights through precise adjustments of individual wingbeats. Surprisingly, motor cortical activity was not dominated by the global wingbeat cycle. Instead, individual neurons were sparsely active, exhibiting mixed selectivity for specific flight kinematics combined with variable entrainment to the wingbeat phase reaching millisecond-scale precision. This yielded a high-dimensional population regime driven by low shared variance across wingbeats, with successive wingbeats occupying distinct neural population states. Our findings reveal that during complex natural behavior the mammalian motor cortex operates in a high-dimensional computational regime that challenges prevailing views of motor cortical computation and underscores the importance of studying ethologically relevant behaviors to uncover neural principles governing brain function.

neuroscience↗

Serotonergic modulation of motor subspace dynamics drives a sleep-independent quiescent state

The dorsal raphe nucleus (DRN) serotonergic (5-HT) system has been implicated in regulating sleep and motor control; however, its specific role remains controversial. In this study, we found that optogenetic activation of DRN 5-HT neurons in larval zebrafish induced a quiescent state and a reduced response to acoustic stimuli. Unlike sleep, the induced quiescent state was not accompanied by a loss of postural control, and nighttime activation of DRN 5-HT neurons led to a subsequent sleep rebound. Whole brain light field imaging combined with demixed principal component analysis (dPCA) revealed distinct neural subspaces related to DRN activation, sound responses, and motor activity. DRN 5-HT activation selectively modulated the motor-related subspace while leaving the sound-evoked subspace unaffected. Unlike DRN activation, sleep induced by mepyramine significantly altered sound-evoked neuronal activity patterns. Further analysis demonstrated that serotonin had a graded effect on the motor subspace, wherein downstream neurons responsible for particular bout types were more significantly influenced. Embedding motor population activity in a curved geometric space revealed that the degree of curvature scales with behavioral suppression across animals, providing a quantitative signature of the quiescent state. Together, these results elucidate that serotonergic modulation promotes behavioral quiescence through selective regulation of motor populations.

neuroscience↗

Translation efficiency covariation across cell types is a conserved organizing principle of mammalian transcriptomes

Characterizing shared patterns of RNA expression between genes across conditions has led to the discovery of regulatory networks and novel biological functions. However, it is unclear if such coordination extends to translation. Here, we uniformly analyzed 3,819 ribosome profiling datasets from 117 human and 94 mouse tissues and cell lines. We introduce the concept of translation efficiency covariation (TEC), identifying coordinated translation patterns across cell types. We nominate candidate mechanisms driving shared patterns of translation regulation. TEC is conserved across human and mouse cells and uncovers gene functions that are not evident from RNA or protein co-expression. Moreover, our observations indicate that proteins that physically interact are highly enriched for positive covariation at both translational and transcriptional levels. Our findings establish TEC as a conserved organizing principle of mammalian transcriptomes.

bioinformatics↗

All-optical interrogation of brain-wide activity in freely swimming larval zebrafish

We introduce an all-optical technique that enables volumetric imaging of brain-wide calcium activity and targeted optogenetic stimulation of specific brain regions in freely swimming larval zebrafish. The system consists of three main components: a 3D tracking module, a dual color fluorescence imaging module, and a real-time activity manipulation module. Our approach uses a sensitive genetically encoded calcium indicator in combination with a long Stokes shift red fluorescence protein as a reference channel, allowing the extraction of Ca2+ activity from signals contaminated by motion artifacts. The method also incorporates rapid 3D image reconstruction and registration, facilitating real-time selective optogenetic stimulation of different regions of the brain. By demonstrating that selective light activation of the midbrain regions in larval zebrafish could reliably trigger biased turning behavior and changes of brain-wide neural activity, we present a valuable tool for investigating the causal relationship between distributed neural circuit dynamics and naturalistic behavior. HighlightsO_LIWe develop an all-optical technique that enables simultaneous whole brain imaging and optogenetic manipulation of selective brain regions in freely behaving larval zebrafish. C_LIO_LIA combination of a genetically encoded calcium indicator and a long Stokes-shift red fluorescence protein, together with the adaptive filter algorithm, enables us to reliably distinguish calcium activity from motion-induced signal contamination. C_LIO_LIRapid 3D image reconstruction and registration enables real-time targeted optogenetic stimulation of distinct brain regions in a freely swimming larval zebrafish. C_LI

neuroscience↗

The scale-invariant covariance spectrum of brain-wide activity

Understanding neural activity organization is vital for deciphering brain function. By recording whole-brain calcium activity in larval zebrafish during hunting and spontaneous behaviors, we find that the shape of the neural activity space, described by the neural covariance spectrum, is scale-invariant: a smaller, randomly sampled cell assembly resembles the entire brain. This phenomenon can be explained by Euclidean Random Matrix theory, where neurons are reorganized from anatomical to functional positions based on their correlations. Three factors contribute to the observed scale invariance: slow neural correlation decay, higher functional space dimension, and neural activity heterogeneity. In addition to matching data from zebrafish and mice, our theory and analysis demonstrate how the geometry of neural activity space evolves with population sizes and sampling methods, thus revealing an organizing principle of brain-wide activity.

neuroscience↗

Structure and function of diadenylate cyclase DacM from Mycoplasma ovipneumoniae

Cyclic diadenosine monophosphate (c-di-AMP) is a second-messenger nucleotide that is produced by many bacteria. C-di-AMP can not only regulate bacterial growth, cell-wall homeostasis, ion transport and gene transcription, but can also be recognized by multiple sensor / receptor proteins in infected host cells to trigger an innate immune response. Mycoplasma ovipneumoniae causes non-progressive pneumonia in both sheep and goats. Here, we analyzed c-di-AMP signaling in M. ovipneumoniae, which is a genome-reduced obligately pathogenic bacterium. Our results demonstrate that these bacteria can produce c-di-AMP, and we could identify the diadenylate cyclase, which was named DacM. The enzyme was found to utilize both ATP and ADP to synthesize c-di-AMP, resembling CdaM from a novel family of diadenylate cyclases first found in Mycoplasma pneumoniae. Furthermore, we present the crystal structures of DacM in the apo state and substrate-bound state at 3 [A] and 1.9 [A] resolution, respectively. Mutation of residues Asp112, Gly113, Tyr128, Phe129, and Arg143 surrounding the active sites to Ala were lethal to DacM enzymatic activity. These structures provide valuable insights into the biochemistry of c-di-AMP, and offer a basis for the structure-based design of new drugs for animal husbandry.

pathology↗

AI-driven high-throughput automation of behavioral analysis and dual-channel wireless optogenetics for multiplexing brain dynamics

Advances in behavioral optogenetics are limited by the absence of high-throughput pipelines for the automated analysis of behavior in freely behaving animals. Although a variety of AI algorithms has been proposed that enable automation of behavioral analysis, existing methods are generally low-throughput. In addition, optogenetic manipulation of neural circuits typically requires physical tethers to light sources, which limits the number of brain areas that can be targeted and thus constrains behavioral testing. Here, we develop a new wireless platform that combines a battery-free dual-channel optogenetic implant with an AI algorithm for high-throughput behavioral analysis. In our platform, a customized AI algorithm detected and quantified freezing behavior of rats that had undergone fear conditioning. Notably, our platform allows up to four enclosures to be monitored simultaneously. Wireless dual-channel optogenetic devices were implanted in the basolateral amygdala (BLA) to permit independent modulation of BLA principal neurons (red light, AAV-CaMKII-JAWS) or BLA interneurons (blue light, AAV-mDlx-ChR2) in freely behaving animals. In vivo validation with behaving rats demonstrates the utility of the telemetry system for large-scale optogenetic studies. SignificanceAI algorithms can enable automation of behavioral analysis and thereby facilitate the progress on behavioral optogenetics. Successful integration of advanced wireless dual-channel optoelectronic devices with biological systems can also yield new tools and techniques for neuroscience research, particularly in the context of techniques for optogenetics. Here, we propose a new approach that combines an advanced AI algorithm with a low power wireless telemetry system, yielding powerful capabilities in the understanding of brain functions and the evaluation of the behavioral consequences of neural circuit manipulations. In vivo studies using optimized systems demonstrate high-throughput automation of behavioral manipulation and analysis via AI-powered wireless telemetry.

neuroscience↗

Maternal vitamin D deficiency increases the risk of obesity in male mice offspring by affecting the immune response

Recently, many epidemiological and animal studies have indicated that obesity have their origin in the early stages of life including the inappropriate balance of some nutrients, the objective of this study is to determine the risk of obesity in male mice offspring as a consequence of maternal VD deficiency-mediated disordering of the immune response. Four-week-old C57BL/6J female mice were fed VD-deficient or normal reproductive diets during pregnancy and lactation. Their male offspring were weighted and euthanized after being fed control and high-fat diets (HFD) for 16 weeks starting at the weaning. The serum was collected for biochemical analyses. Epididymal (eWAT) and inguinal (iWAT) white adipose tissues were excised for histological examination, immunohistochemistry, gene expressions of inflammatory factors, and for determining the proportions of immune cells by flow cytometry. Insufficient maternal VD intake exacerbated the development of obesity both in non-obese and obese male offspring as evidenced by larger adipose cells and abnormal glucose and lipid metabolisms. Also, the expression of proinflammatory cytokine genes was increased and that of anti-inflammatory cytokines was decreased in maternal VD-deficient groups in the eWAT and/or iWAT. This was accompanied by higher levels of TNF- or/and INF-{beta}, and lower levels of IL-4 and IL-10. Insufficient maternal VD intake was also observed to induce a shift in the profiles of immune cells in the eWAT and/or iWAT, resulting in increased percentages of M1 macrophage, ATDCs, and CD4+ and CD8+ T cells, but caused a significant decrease in the percentage of M2 macrophages, both in non-obese and obese male offspring. All these changes in the immune cell profile were more obvious in the eWAT than in the iWAT. These results indicated that insufficient maternal VD intake promoted the development of obesity in male offspring by modulating the immune cell populations and causing a polarization in the adipose depots. ImportanceEvidence in this study has indicated that insufficient maternal VD intake promotes the development of obesity in the male offspring by modulating the recruitment of immune cell populations and their polarization as well as the expression and secretion of proinflammatory adipokines in the adipose depots in a weight-independent manner, which is more obvious in eWAT than that in the iWAT.

immunology↗

Characterization of a novel NDM-5-harboring plasmid from a carbapenem-resistant Escherichia coli isolate from China

A carbapenem-resistant Escherichia coli (sequence type 5415) strain was isolated from a male patient. S1-PFGE and Southern blotting showed that the blaNDM-5 gene was located on a novel 66-kb IncFII [F2:A-:B-] plasmid. Conjugation assays revealed that the blaNDM-5-bearing plasmid was self-transferrable. Genomic sequencing and comparative analysis suggested that plasmid p2947-NDM5 likely originated from a combination of an IncFII-type backbone and the blaNDM-5 flanking genetic elements. This study highlights the genetic complexity of an NDM-5 carbapenemase and the urgent need for continuous active monitoring. IMPORTANCECarbapenem resistance due to the NDM enzyme has become a serious clinical problem in medical care and public health. We here identified a blaNDM-5-positive E. coli strain ST5414. The blaNDM-5 gene was located on a novel self-transferrable IncFII type plasmid p2947-NDM5. Genomic sequencing and comparative analysis suggested that plasmid p2947-NDM5 likely originated from a combination of an IncFII-type backbone and the blaNDM-5 flanking genetic elements. The genetic context of NDM-5 is highly similar to that of animal origins, and we speculate that the blaNDM-harboring IncFII plasmid has a potential risk of being transmitted from animals to humans and should be paid more attention. Our findings highlight the threat of NDM-5 carbapenemase circulation and the urgency of stringent surveillance and control measures.

genomics↗