Dynamics of population activity in rat sensory cortex: Network correlations predict anatomical arrangement and information content

To study the spatiotemporal dynamics of neural activity in a cortical population, we implanted a 10 × 10 microelectrode array in the vibrissal cortex of urethane-anesthetized rats. We recorded spontaneous neuronal activity as well as activity evoked in response to sustained and brief sensory stimulation. To quantify the temporal dynamics of activity, we computed the probability distribution function (PDF) of spiking on one electrode given the observation of a spike on another. The spike-triggered PDFs quantified the strength, temporal delay, and temporal precision of correlated activity across electrodes. Nearby cells showed higher levels of correlation at short delays, whereas distant cells showed lower levels of correlation, which tended to occur at longer delays. We found that functional space built based on the strength of pairwise correlations predicted the anatomical arrangement of electrodes. Moreover, the correlation profile of electrode pairs during spontaneous activity predicted the “signal” and “noise” correlations during sensory stimulation. Finally, mutual information analyses revealed that neurons with stronger correlations to the network during spontaneous activity, conveyed higher information about the sensory stimuli in their evoked response. Given the 400-μm-distance between adjacent electrodes, our functional quantifications unravel the spatiotemporal dynamics of activity among nearby and distant cortical columns

Information processing across behavioral states: Modes of operation and population dynamics in rodent sensory cortex

Animals live in a complex and changing environment with various degrees of behavioral demands. In rodents, the behavioral states can change from sleep and quiet wakefulness to active exploration of the environment which is often manifested by whisking and locomotion. Efficient information processing is more important in some of these behavioral states such as during episodes of sensory decision-making, and specific cortical areas are expected to receive priority of processing depending on the behavioral context. It is therefore not surprising that the behavioral state affects the responsiveness of individual cortical neurons and the dynamics of neuronal population activity. Here, we review the circuit mechanisms that determine the operating mode of the sensory cortex. We explore state modulations across multiple sensory modalities, but maintain a focus on whisker-mediated behaviors, the processing of information in the vibrissal somatosensory cortex and its transfer to higher order areas. Finally, we suggest a rodent sensory prioritization paradigm to further probe the link between behavioral state, neuronal population dynamics and coding efficiency.Supported by an Australian Research Council (ARC) Discovery Project (DP170100908), the ARC Centre of Excellence for Integrative Brain Function (CE140100007), an NH&MRC Project grant (1124411), and a scholarship from the Iran’s National Elites Foundation to MMS

Auraptene-induced cytotoxicity mechanisms in human malignant glioblastoma (U87) cells

Glioblastoma multiforme (GBM), like the devastating type of astrocytic tumors, is one of the most challenging cancers to treat owing to its aggressive nature. Auraptene, as a prenyloxy coumarin from citrus species, represents antioxidant and antitumor activities; however, the underlying antitumor mechanisms of auraptene against GBM remain unclear. The present study aimed to evaluate the cytotoxic and apoptogenic effect s of auraptene, as a promising natural product, and the possible signaling pathways affected in human malignant GBM (U87) cells. Reactive oxygen species (ROS) production significantly decreased in the first 2, and 6 hours after treatment with auraptene however, ROS levels increased in other incubation times (8 and 24 hours), dramatically. N-acetyl-cysteine (NAC) markedly attenuated auraptene–induced ROS production, and consequently reversed auraptene–induced cytotoxicity in 8 and 24 hours after treatment, as well. Induction of apoptosis occurred in the first 24- and 48-hours concentration-dependently. The qRT-PCR showed an up-regulation in p21, CXCL3, and a down-regulation in Cyclin D1 genes expression. Western blot analysis confirmed the up-regulation of the Bax/Bcl-2 ratio protein levels concentration-dependently. Hence, this study collectively revealed that the increase in ROS level is at least one of the mechanisms associated with auraptene-induced GBM cell toxicity as well as the induction of apoptosis through Bax/Bcl-2 modulation and genes expression involved that contribute to the cytotoxicity of auraptene in U87 cells. So, auraptene might be utilized as a potential novel anti-GBM agent after further studies

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)