Neuroscientists endeavor to unravel the mysteries of brain functions and dysfunctions. A common research strategy involves measuring specific parameters across various conditions. These measurements are then typically repeated, averaged, and used to infer general patterns or rules. The act of averaging data is an ancient practice; for instance, early astronomers in Babylonian, Chinese, and Indian cultures implicitly averaged observations of celestial phenomena to predict significant periods, such as those crucial for agriculture. Averaging is a sound approach when the process being studied follows to a mathematical function, represented as y = f(x), where f is a very general function. This is true even if the exact function is not known at the outset of the experiments. Implicit in this method is the assumption that any variations in measurements arise from imperfections in the recording process since a consistent mathematical rule suggests that identical inputs should always yield the same output. In ess...

I am always marveled by the brain’s vast capabilities. Each discovery, each revelation, seems to open a door only to reveal myriad others yet unopened. The brain, with its vast intricacies, consistently reminds us that its complexity transcends the limits of our imagination. It is in this spirit that I wish to introduce “Brain Mysteries: Complexity Beyond Imagination” in eNeuro . All neuroscientists have been contributing for decades to the mapping of brain networks and to the unraveling of its codes. While every stride has been fruitful in terms …

Animals exhibit context-dependent behavioral decisions that are mediated by specific motor circuits. In social species these decisions are often influenced by social status. Although social status-dependent neural plasticity of motor circuits has been investigated in vertebrates, little is known of how cellular plasticity translates into differences in motor activity. Here, we used zebrafish ( Danio rerio ) as a model organism to examine how social dominance influences the activation of swimming and the Mauthner mediated startle escape behaviors. We show that the status-dependent shift in behavior patterns whereby dominants increase swimming and reduce sensitivity of startle escape while subordinates reduce their swimming and increase startle sensitivity is regulated by the synergistic interactions of dopaminergic, glycinergic and GABAergic inputs to shift the balance of activation of the underlying motor circuits. This shift is driven by socially induced differences in expression of dopaminergic receptor ...

Psychotic drugs such as ketamine induce symptoms close to schizophrenia and stimulate the production of γ oscillations, as also seen in patients, but the underlying mechanisms are still unclear. Here, we have used computational models of cortical networks generating γ oscillations, and have integrated the action of drugs such as ketamine to partially block NMDA receptors (NMDARs). The model can reproduce the paradoxical increase of γ 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 channels are blocked, an increase of γ power is observed altogether with an increase of network responsiveness. However, this responsiveness increase applies not only to γ states, but also to asynchronous states with no apparent γ. We conclude that NMDA antagonists induce an increased excitability state, which may or may not pr...

Migratory locusts enter a reversible hypometabolic coma to survive environmental anoxia, wherein the cessation of 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 with MIA. Specifically, although 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 injuries were associated wi...

Converging evidence indicates the 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. The study was conducted in a crossover and double-blind design. Twenty-six healthy sedentary individuals (13 women and 13 men) performed a motor learning task and received a cortical excitability assessment before and after a single session of low-, moderate-, and high-intensity aerobic exercise or a control intervention. The study revealed that motor learning performance and cortical excitability were significantly enhanced in the moderate-intensity aerobic exercise, compared wi...

During the development of the cerebral cortex, N-cadherin plays a crucial role in facilitating radial migration by enabling cell-to-cell adhesion between migrating neurons and radial glial fibers or Cajar–Reztius cells. ADP ribosylation factor 4 (Arf4) and Arf5, which belong to the Class II Arf small GTPase subfamily, control membrane trafficking in the endocytic and secretory pathways. However, their specific contribution to cerebral cortex development remains unclear. In this study, we sought to investigate the functional involvement of Class II Arfs in radial migration during the layer formation of the cerebral cortex using mouse embryos and pups. Our findings indicate that knock-down of Arf4, but not Arf5, resulted in the stalling of transfected neurons with disorientation of the Golgi in the upper intermediate zone (IZ) and reduction in the migration speed in both the IZ and cortical plate (CP). Migrating neurons with Arf4 knock-down exhibited cytoplasmic accumulation of N-cadherin, along with disturb...

The objective of this work was to develop a deep learning-based automatic system with reliable performance in detecting interictal epileptiform discharges (IEDs) from scalp electroencephalograms (EEGs). 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 nine deep neural networks (DNNs) were trained for the multiclassification of IED, artifact, and background. The fitted IED detectors were then evaluated on 78 EEG recordings with IED events fully annotated by three 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 estima...

The retina has diverse neuronal cell types derived from a common pool of retinal progenitors. Many molecular drivers, mostly transcription factors, have been identified to promote different cell fates. In Drosophila , atonal is required for specifying photoreceptors. In mice, there are two closely related atonal homologs, Atoh1 and Atoh7 . While Atoh7 is known to promote the genesis of retinal ganglion cells, there is no study on the function of Atoh1 in retinal development. Here, we crossed Atoh1Cre/+ mice to mice carrying a Cre-dependent TdTomato reporter to track potential Atoh1 -lineage neurons in retinas. We characterized a heterogeneous group of TdTomato+ retinal neurons that were detected at the postnatal stage, including glutamatergic amacrine cells, AII amacrine cells, and BC3b bipolar cells. Unexpectedly, we did not observe TdTomato+ retinal neurons in the mice with an Atoh1-FlpO knock-in allele and a Flp-dependent TdTomato reporter, suggesting Atoh1 is not expressed in the mouse retina. Consiste...

Manipulating working memory (WM) is a central yet challenging notion. Previous studies suggest that WM items with varied memory strengths reactivate at different latencies, supporting a time-based mechanism. Motivated by this view, here we developed a purely bottom-up “Leader–Follower” behavioral approach to manipulate WM in humans. Specifically, task-irrelevant flickering color disks that are bound to each of the memorized items are presented during the delay period, and the ongoing luminance sequences of the color disks follow a Leader–Follower relationship, that is, a hundreds of milliseconds temporal lag. We show that this dynamic behavioral approach leads to better memory performance for the item associated with the temporally advanced luminance sequence (Leader) than the item with the temporally lagged luminance sequence (Follower), yet with limited effectiveness. Together, our findings constitute evidence for the essential role of temporal dynamics in WM operation and offer a promising, noninvasive ...