Biology subjects

Pu, Y.

Publications and source records attributed to Pu, Y..

5 recordsLinked to original sources

bioRxiv2018

Human hippocampal high-gamma activity during rest periods in a virtual navigation task

In rodents, hippocampal cell assemblies formed during learning of a navigation task are observed to re-emerge during resting (offline) periods, accompanied by high-frequency oscillations (HFOs). This phenomenon is believed to reflect mechanisms for strengthening newly-formed memory traces. Using magnetoencephalography recordings and a beamforming source location algorithm (synthetic aperture magnetometry), we investigated high-gamma (80 - 140 Hz) oscillations in the hippocampal region in 18 human participants during inter-trial rest periods in a virtual navigation task. We found right hippocampal gamma oscillations mirrored the pattern of theta power in the same region during navigation, varying as a function of environmental novelty. Gamma power during inter-trial rest periods was positively correlated with theta power during navigation in the first training set when the environment was new and predicted faster learning in the subsequent training set two where the environment became familiar. These findings provide evidence for human hippocampal reactivation accompanied by high-gamma activities immediately after learning and establish a link between hippocampal high-gamma activities and memory consolidation.

neuroscience↗

bioRxiv2017

Extensive sex differences at the initiation of genetic recombination

Homologous recombination in meiosis is initiated by programmed DNA double strand breaks (DSBs) and DSB repair as a crossover is essential to prevent chromosomal abnormalities in gametes. Sex differences in recombination have been previously observed by analyses of recombination end-products. To understand when and how sex differences are established, we built genome-wide maps of meiotic DSBs in both male and female mice. We found that most recombination initiates at sex-biased DSB hotspots. Local context, the choice of DSB targeting pathway and sex-specific patterns of DNA methylation give rise to these differences. Sex differences are not limited to the initiation stage, as the rate at which DSBs are repaired as crossovers appears to differ between the sexes in distal regions. This uneven repair patterning may be linked to the higher aneuploidy rate in females. Together, these data demonstrate that sex differences occur early in meiotic recombination.

genomics↗

bioRxiv2017

Dynamic protein aggregation regulates bacterial dormancy depth critical for antibiotic tolerance

The ability of some bacteria within a population to tolerate antibiotic treatment is often attributed to prolonged bacterial infection1-3. Unlike antibiotic resistance, which generally results from genetic mutations or plasmid transfer4,5, antibiotic tolerance usually refers to the phenomenon that a subgroup of cells can survive high dose antibiotic treatment as a result of phenotypic heterogeneity6,7. Previous studies mainly associate antibiotic tolerance with cell dormancy, by hypothesizing that the lethal effects of antibiotics are disabled due to the extremely slow metabolic and proliferation rates in dormant bacteria 8,9. However, less is known about how surviving bacteria subsequently escape from the dormant state and resuscitate, which is equally important for disease recurrence. Here we monitored the process of bacterial antibiotic tolerance and regrowth at the single-cell level, and found that each individual survival cell shows different dormancy depth, which in return regulates whether and when it can resume growth after removal of antibiotic. The persister cells are considered to be in shallow dormancy depth, while the viable but non-culturable cells (VBNC cells) are in deep dormancy depth. We further implemented time-lapse fluorescent imaging and biochemical analysis to establish that dynamic endogenous protein aggregation is an important indicator of bacterial dormancy depth. For cells to leave the dormant state and resuscitate, clearance of cellular protein aggregates and recovery of proteostasis are required. Through additional mutagenesis studies, we found the ability to recruit functional DnaK-ClpB machineries, which facilitate protein disaggregation in an ATP-dependent manner, determines the timeline (whether and when) for bacterial regrowth. Better understanding of the key factors regulating bacterial regrowth after surviving antibiotic attack could lead to new therapeutic strategies for combating bacterial antibiotic tolerance.

microbiology↗

bioRxiv2017

Gated Coupling of Dopamine and Neuropeptide Signaling Underlies Perceptual Processing of Appetitive Odors in Drosophila

How olfactory stimuli are perceived as meaningful cues for specific appetitive drives remains poorly understood. Here we show that despite their enormous diversity, Drosophila larvae can discriminatively respond to food-related odor stimuli based on both qualitative and quantitative properties. Perceptual processing of food scents takes place in a neural circuit comprising four dopamine (DA) neurons and a neuropeptide F (NPF) neuron per brain hemisphere. Furthermore, these DA neurons integrate and compress inputs from second-order olfactory neurons into one-dimensional DA signals, while the downstream NPF neuron assigns appetitive significance to limited DA outputs via a D1-type DA receptor (DoplR1)-mediated gating mechanism. Finally, Dop1R, along with a G{beta}13F/Irk2-mediated inhibitory and a Gs-mediated excitatory pathway, underlie a binary precision tuning apparatus that restricts the excitatory response of NPF neurons to DA inputs that fall within an optimum range. Our findings provide fresh molecular and cellular insights into cognitive processing of olfactory cues.

neuroscience↗

bioRxiv2017

Intrinsic Hippocampal-Caudate Interaction Correlates with Human Navigation

It has been indicated that both egocentric and allocentric representation systems exist in parallel, and combine to support spatial navigation according to the task. Identifying the neuronal mechanisms and functional roles of the interactions between the two systems promises to provide new insights into the organization of human navigation network. Here we combined resting-state fMRI and behavioral tasks to investigate how the core structures of these systems (i.e., hippocampus and caudate) functionally interact, and further examined their behavioral relevance in navigation in healthy young adults (N = 190). We found a slightly positive connectivity between the hippocampus and caudate (especially in good navigators), suggesting an effective hippocampal-caudate cross talk, which may facilitate the functional integration of the two systems. Interestingly, the hippocampal-caudate interaction correlated with better self-reported navigation ability. Moreover, using an extra 3D pointing task in virtual reality, we found that individuals behavioral performance could be largely predicted by the hippocampal-caudate interactions. Overall, our study demonstrated the intrinsic interaction between two representation systems of the navigation network and its functional roles in behaviors, and further study on dynamic interaction would help us understand better their role in normal aging and psychiatric disorders.

neuroscience↗