Antibody-based imaging techniques rely on reagents whose performance may be application-specific. Because commercial antibodies are validated for only a few purposes, users interested in other applications may have to perform extensive in-house antibody testing. Here we present a novel application-specific proxy screening step to efficiently identify candidate antibodies for array tomography (AT), a serial section volume microscopy technique for high-dimensional quantitative analysis of the cellular proteome. To identify antibodies suitable for AT-based analysis of synapses in mammalian brain, we introduce a heterologous cell-based assay that simulates characteristic features of AT, such as chemical fixation and resin embedding that are likely to influence antibody binding. The assay was included into an initial screening strategy to generate monoclonal antibodies that can be used for AT. This approach simplifies the screening of candidate antibodies and has high predictive value for identifying antibodies...

Extracting common patterns of neural circuit computations in the autism spectrum and confirming them as a cause of specific core traits of autism is the first step towards identifying cell- and circuit-level targets for effective clinical intervention. Studies in humans with autism have identified functional links and common anatomical substrates between core restricted behavioral repertoire, cognitive rigidity, and over-stability of visual percepts during visual rivalry. To study these processes with single-cell precision and comprehensive neuronal population coverage, we developed the visual bi-stable perception paradigm for mice based on ambiguous moving plaid patterns consisting of two transparent gratings drifting at an angle of 120°. This results in spontaneous reversals of the perception between local component motion (plaid perceived as two separate moving grating components) and integrated global pattern motion (plaid perceived as a fused moving texture). This robust paradigm doesn’t depend on the...

Psychotic drugs such as ketamine induce symptoms close to schizophrenia, and stimulate the production of gamma oscillations, as also seen in patients, but the underlying mechanisms are still unclear. Here, we have used computational models of cortical networks generating gamma oscillations, and have integrated the action of drugs such as ketamine to partially block n-methyl-d-Aspartate (NMDA) receptors. The model can reproduce the paradoxical increase of gamma oscillations by NMDA-receptor antagonists, assuming that antagonists affect NMDA receptors with higher affinity on inhibitory interneurons. We next used the model to compare the responsiveness of the network to external stimuli, and found that when NMDA channnels are blocked, an increase of gamma power is observed altogether with an increase of network responsiveness. However, this responsiveness increase applies not only to gamma states, but also to asynchronous states with no apparent gamma. We conclude that NMDA antagonists induce an increased exc...

Electro-acupuncture (EA) is widely applied in clinical therapy for spinal cord injury (SCI). However, the associated molecular mechanism has yet to be elucidated. The current study aimed to investigate the underlying mechanism of EA in neurological repair after SCI. Firstly, we investigated the role of EA in the neurological repair of the SCI rat model. The expression levels of Human antigen R (HuR) and Kruppel-like factor 9 (KLF9) in spinal cord tissues were quantified after EA treatment. Secondly, we carried out bioinformatics analysis, RNA pull-down assay, RNA immunoprecipitation, and luciferase reporter gene assay to verify the binding of HuR and KLF9 mRNA for mRNA stability. Lastly, HuR inhibitor CMLD-2 was used to verify the enhanced effect of EA on neurological repair after SCI via the HuR/KLF9 axis. Our data provided convincing evidence that EA facilitated the recovery of neuronal function in SCI rats by reducing apoptosis and inflammation of neurons. We found that EA significantly diminished the S...

SQUID-based magnetoencephalography has been shown to improve the diagnosis and surgical treatment decision for presurgical evaluation of drug-resistant epilepsy. Still, its use remains limited due to several constraints such as cost, fixed helmet size and obligation of immobility. A new generation of sensors, the optically pumped magnetometers (OPMs), could overcome these limitations. In this study, we validate the ability of Helium-based OPM (4He-OPM) sensors to record epileptic brain activity thanks to simultaneous recordings with intracerebral EEG (stereotactic EEG, SEEG). We recorded simultaneous SQUIDs-SEEG and 4He-OPM-SEEG signals in one patient during two sessions. We show that epileptic activities on intracerebral EEG can be recorded by OPMs with a better signal-to noise ratio than classical SQUIDs. The OPM sensors open new venues for the widespread application of magnetoencephalography in the management of epilepsy and other neurological diseases and fundamental neuroscience. Significance Stateme...

Migratory locusts enter a reversible hypometabolic coma to survive environmental anoxia, wherein the cessation of central nervous system (CNS) activity is driven by spreading depolarization (SD). While glycolysis is recognized as a crucial anaerobic energy source contributing to animal anoxia tolerance, its influence on the anoxic SD trajectory and recovery outcomes remains poorly understood. We investigated the effects of varying glycolytic capacity on adult female locust anoxic SD parameters, using glucose or the glycolytic inhibitors 2-deoxy-D-glucose (2DG) or monosodium iodoacetate (MIA). Surprisingly, 2DG treatment shared similarities with glucose yet had opposite effects compared to MIA. Specifically, though SD onset was not affected, both glucose and 2DG expedited the recovery of CNS electrical activity during reoxygenation, whereas MIA delayed it. Additionally, glucose and MIA, but not 2DG, increased tissue damage and neural cell death following anoxia-reoxygenation. Notably, glucose-induced injuri...

Objectives: Converging evidence indicates beneficial effects of aerobic exercise on motor learning performance. Underlying mechanisms might be an impact of aerobic exercise on neuroplasticity and cortical excitability. Evidence suggests that motor learning and cortical excitability alterations correlate with the intensity of aerobic exercise and the activity level of participants. Thus, this study aims to investigate the effects of different aerobic exercise intensities on motor learning and cortical excitability in sedentary individuals. Methods : The study was conducted in a cross-over and double-blind design. 26 healthy sedentary individuals (13 women and 13 men) performed a motor learning task and received cortical excitability assessment before and after a single session of low-, moderate-, high-intensity aerobic exercise or a control intervention. Results : The study revealed that motor learning performance and cortical excitability were significantly enhanced in the moderate-intensity aerobic exerci...

Most human navigation studies in MRI rely on virtual navigation. However, the necessary supine position in MRI makes it fundamentally different from daily ecological navigation. Nonetheless, until now, no study has assessed whether differences in physical body orientation (BO) affect participants’ experienced BO during virtual navigation. Here, combining an immersive virtual reality (VR) navigation task with subjective BO measures and implicit behavioral measures, we demonstrate that physical BO (either standing or supine) modulates experienced BO. Also, we show that standing upright BO is preferred during spatial navigation: participants were more likely to experience a standing BO and were better at spatial navigation when standing upright. Importantly, we report that showing a supine virtual agent reduces the conflict between the preferred BO and physical supine BO. Our study provides critical, but missing, information regarding experienced BO during virtual navigation, which should be considered cautio...

Objective: To develop a deep learning-based automatic system with reliable performance in detecting interictal epileptiform discharges (IEDs) from scalp electroencephalograms (EEGs). Methods: For the present study, 484 raw scalp EEG recordings were included, standardized, and split into 406 for training and 78 for testing. Two neurophysiologists individually annotated the recordings for training in channel-wise manner. Annotations were divided into segments, on which 9 deep neural networks (DNNs) were trained for the multi-classification of IED, artifact and background. The fitted IED detectors were then evaluated on 78 EEG recordings with IED events fully annotated by 3 experts independently (majority agreement). A two-montage-based decision mechanism (TMDM) was designed to determine whether an IED event occurred at a single time instant. Area under the precision-recall curve (AUPRC), as well as false positive rates, F1 scores, and Kappa agreement scores for sensitivity = 0.8 were estimated. Results: In...

Rhythms are a common feature of brain activity. Across different types of rhythms, the phase has been proposed to have functional consequences, thus requiring its accurate specification from noisy data. Phase is conventionally specified using techniques that presume a frequency band-limited rhythm. However, in practice, observed brain rhythms are typically nonsinusoidal and amplitude modulated. How these features impact methods to estimate phase remains unclear. To address this, we consider three phase estimation methods, each with different underlying assumptions about the rhythm. We apply these methods to rhythms simulated with different generative mechanisms and demonstrate inconsistency in phase estimates across the different methods. We propose two improvements to the practice of phase estimation: (1) estimating confidence in the phase estimate, and (2) examining the consistency of phase estimates between two (or more) methods.