Reviews & Analysis

Sulaman et al. detail the neuronal underpinnings of sleep–wake states and discuss their intersection with hunger, fear and thermoregulatory circuits. They propose a de-arousal model for sleep initiation and highlight lingering questions in the field.

The use of field-standard approaches in neuroscience and psychology can exclude participants from research, biasing our understanding of brain–behavior relations. Here the authors discuss how we might address inequity in our scientific methodology.

Despite rich behavioral evidence, it is unclear how the brain expands its behavior repertoire. By building theoretical models with a deep reinforcement learning algorithm, I show that the brain composes a behavior to solve a novel task by combining previously acquired skills and augmenting their variability.

The authors summarize changes in circuits after spinal cord injury and current strategies to target these circuits in order to improve recovery, but also advocate for new concepts of reorganizing circuits informed by multi-omic single-cell atlases.

Scheggia et al.¹ have established a behavioral paradigm to explore preferences for ‘altruistic’ or ‘selfish’ choice behavior in mice. The results suggest that altruistic behavior develops through reinforcement learning driven by social rewards, which is controlled by interactions between the basolateral amygdala and prelimbic cortex.

Psychedelics are serotonergic drugs that have therapeutic potential. This Review article provides an integrative perspective on the basic neurobiology underlying the actions of psychedelics and highlights open questions in the field.

How genetic and environmental risk factors interact to trigger the development of post-traumatic stress disorder (PTSD) remains largely unknown. Seah et al. model stress hypersensitivity as a potential mechanism by examining transcriptomic responses to glucocorticoids in neurons derived from individuals with PTSD.

Learning requires new oligodendrogenesis, but how myelin patterns change during learning is unclear. Bacmeister et al. show that motor learning induces phase-specific changes in myelination on behaviorally activated axons that correlate with motor performance, suggesting myelin remodeling is involved in learning.

Although axonal GABA_A receptors are thought to cause presynaptic inhibition, we show that instead they often facilitate sodium channel activation at nodes of myelinated axons. This facilitation determines which branches of sensory axons conduct action potentials to motor neurons, enabling computation at the level of the node to regulate sensory feedback.

Frontal cortex activity contains a mixture of signals for different behavioral and cognitive processes. Analysis of 20,000 frontal cortical neurons during a tactile decision-making task revealed functional clusters encoding specific behavioral variables. By manipulating the inputs to frontal cortex, we attributed the origin of their activities to inputs from the thalamus.

This Review organizes models of cognitive maps into a clear ontology. This ontology reveals parallels between existing empirical results and implies new approaches to understand hippocampal–cortical interactions and beyond.

We studied how the sex of human experimenters affected mouse behaviors and brain functions under normal conditions and in the context of ketamine administration. Identifying such unknown unknowns was critical to understanding how, specifically and quantitatively, they affected experimental outcomes, which led to fresh insight into ketamine’s mechanism as an antidepressant drug.

Moscarello and Penzo propose that mutually inhibitory circuits within the central nucleus of the amygdala implement a ‘winner-takes-all’ mechanism that guides transitions across defensive modes defined by threat-imminence theory.

Studying the natural wanderings of the living brain is extremely challenging. Bolt et al. describe a new framework for considering the brain’s intrinsic activity based on the geophysical concepts of standing and traveling waves.

The language network in the brain shows similar properties across 45 languages spanning 12 language ‘families’. The language areas are lateralized to the left hemisphere, selective for language, and strongly functionally inter-connected. Variability among speakers of different languages is similar to the variability that has been reported among English speakers.

This Review provides a comprehensive overview of presynaptic applications of optogenetic tools, including the associated challenges, current limitations and future directions for this approach.

A new study shows that infra-slow cortical norepinephrine oscillations shape the micro-structure of sleep and transitions to micro-arousals, wakefulness or rapid eye movement (REM) sleep. Prolonged descending phases of these oscillations promote the occurrence of spindle-rich intermediate sleep, which is involved in memory consolidation.

During cortical development, the generation of neurons from progenitors coincides with increasing vascularization and oxygen levels in the fetal brain and the transition from anaerobic to aerobic metabolism. Dong et al. identify lactate, a metabolite of anaerobic glycolysis, as a multifunctional regulator that coordinates synchrony of cortical neurogenesis and angiogenesis.

A new cell state of disease-associated oligodendrocytes (DOLs) has been identified, which presents a transcriptional program that is probably driven by neuroinflammation and is shared among different non-immune glial cells across multiple pathologies of the central nervous system.

Epilepsy is the most common childhood neurological disease, and nearly 20% of affected children develop drug-resistant childhood epilepsy (DRCE). Using single-cell analysis methods, Kumar et al. have identified pro-inflammatory interactions between microglia and T cells in brain tissue from individuals with DRCE. This work may help to identify therapeutic targets for DRCE.