Every so often, I conclude that life is not possible. It is not uncommon for me to walk out of a seminar about the pathways and dynamics of biochemical signaling or the structure of biological molecules to conclude that the complexities of life processes defy imagination. Our ability to maintain a sense of wonder about the mysteries of biological mechanisms is what drives us as scientists, as otherwise wresting new insights from the recalcitrant world of interacting pathways would be too frustrating. So all successful biologists must, paradoxically, see both the proverbial forest and their trees, and recognize both the elegant simplicity and the confounds characteristic of living organisms. That sense of mystery and wonder is somewhat at odds with our common sense. It is common sense that is now too often lost, as we grapple with new technologies and large datasets in our science. As scientists, today, we must balance our common sense with our growing reliance on big data to extract the new insights about...

The sensory system allows humans to not only explore the world but also to monitor their own bodies for injury and disease through the sensation of pain. After an injury, signals from the injured tissues travel along the nerves, entering the central nervous system through the spinal cord before going into the brain. In the acute stages, pain modulates behavior in ways that promote healing, including limiting mobility. In most cases, pain resolves as the injury heals, but, in some cases, pain persists and becomes chronic. Chronic pain is a massive issue, affecting up to 20% of Americans and leading to reduced quality of life for those affected. The factors leading to chronic pain are complex, and new approaches are needed to improve understanding of chronic pain and find effective treatments. In the current issue of eNeuro , Haroun et al. (2023) use a new approach to transiently silence sensory neurons in uninjured mice as well as mouse models of acute and chronic pain using a technique known as chemogenet...

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 ...

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...

Commenting about science has risks. Being critical sometimes raises strong opposing reactions. People work so hard and leaders do not like to see their strategies under fire. Critics do not usually provide easy solutions to the problems they raise, and the questions, even if they are right on target, remain largely unanswered. When the stakes are high and massive funds wait to be delivered, the train (or ship), once launched, ought not to derail (nor sink). It must go on, as planned, keeping the initial thrust alive. In terms of management efficacy, a typical reason why the project’s leadership does not answer critiques is to “keep the monkey(s) on the critics’ shoulders” (Oncken and Wass, 1974; Cover, 1999). Being proactive may be a better way to get rid of the monkeys and open a constructive dialogue. The issue then becomes: what could have been done instead, for a better science? This is typically the question that I am asked at the end of my neuro-epistemological talks, or in comments received followi...

Electroacupuncture (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 neurologic repair after SCI. First, we investigated the role of EA in the neurologic repair of the SCI rat model. The expression levels of human antigen R (HuR) and Krüppel-like factor 9 (KLF9) in spinal cord tissues were quantified after treatment. Second, we conducted bioinformatics analysis, RNA pull-down assays, RNA immunoprecipitation, and luciferase reporter gene assay to verify the binding of HuR and KLF9 mRNA for mRNA stability. Last, HuR inhibitor CMLD-2 was used to verify the enhanced effect of EA on neurologic 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 SCI-mediated upreg...

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...

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...