Emerging evidence implicates experience-dependent myelination in learning and memory. However, the specific signals underlying this process remain unresolved. We demonstrate that the neuropeptide dynorphin, which is released from neurons upon high levels of activity, promotes experience-dependent myelination. Following forced swim stress, an experience that induces striatal dynorphin release, we observe

How the patterns of cortex folding are implemented during embryonic development is poorly understood. In this issue of Neuron, Han et al. (2021) establish that a population of neural progenitor cells co-expressing Neurog2 and Ascl1 are key in this process.

In this issue of Neuron, Izadifar et al. (2021) have identified a conserved molecule Wnk as a key regulator in both developmental axon branching and long-term survival of neurons, characterizing its interplay with axon destruction genes including Sarm. The discovery of Wnk will be important to our understanding of neurodevelopmental and neurodegenerative diseases.

Cocaine triggers gene splicing in brain reward circuits, but the mechanisms and importance of this response are unclear. In this issue of Neuron, Xu et al. (2021) show that the histone modification H3K36me3 marks genes spliced in response to cocaine and, using epigenome editing, establish a causal relationship between gene splicing and addiction-related behavioral responses.

Microglial cells perform a plethora of functions in the central nervous system (CNS), involving them in brain development, maintenance of homeostasis in adulthood, and CNS diseases. Significant technical advancements have prompted the development of novel systems adapted to analyze microglia with increasing specificity and intricacy. The advent of single-cell technologies combined with targeted mouse

The human brain undergoes a prolonged period of cortical development that spans multiple decades. During childhood and adolescence, cortical development progresses from lower-order, primary and unimodal cortices with sensory and motor functions to higher-order, transmodal association cortices subserving executive, socioemotional, and mentalizing functions. The spatiotemporal patterning of cortical

The molecular and cellular mechanisms underlying complex axon morphogenesis are still poorly understood. We report a novel, evolutionary conserved function for the Drosophila Wnk kinase (dWnk) and its mammalian orthologs, WNK1 and 2, in axon branching. We uncover that dWnk, together with the neuroprotective factor Nmnat, antagonizes the axon-destabilizing factors D-Sarm and Axundead (Axed) during axon

The role of the cerebellum in predictive motor control and coordination has been thoroughly studied during movements of a single body part. In the real world, however, actions are often more complex. Here, we show that a small area in the rostral anterior interpositus nucleus (rAIN) of the mouse cerebellum is responsible for generating a predictive motor synergy that serves to protect the eye by precisely

Neural representations of visual working memory (VWM) are noisy, and thus, decisions based on VWM are inevitably subject to uncertainty. However, the mechanisms by which the brain simultaneously represents the content and uncertainty of memory remain largely unknown. Here, inspired by the theory of probabilistic population codes, we test the hypothesis that the human brain represents an item maintained

Human accelerated regions (HARs) are the fastest-evolving regions of the human genome, and many are hypothesized to function as regulatory elements that drive human-specific gene regulatory programs. We interrogate the in vitro enhancer activity and in vivo epigenetic landscape of more than 3,100 HARs during human neurodevelopment, demonstrating that many HARs appear to act as neurodevelopmental enhancers

Higher-order projections to sensory cortical areas converge on layer 1 (L1), the primary site for integration of top-down information via the apical dendrites of pyramidal neurons and L1 GABAergic interneurons. Here we investigated the contribution of early thalamic inputs onto L1 interneurons for establishment of top-down connectivity in the primary visual cortex. We find that bottom-up thalamic inputs

Chronic pain is more common in women, however, our understanding of sex-specific differences in pain mechanisms is rudimentary. In this issue of Neuron, Luo et al., (2021) delineate a novel sex-specific neuro-immune pathway contributing to enhanced mechanical pain in females.

In this issue of Neuron, Bonnen et al. (2021) use artificial neural networks to resolve a long-standing controversy surrounding the neurocognitive dichotomy between memory and perception. They show that the perirhinal cortex supports performance on tasks that cannot be solved by the ventral visual stream.

In this issue of Neuron, Norman et al. (2021) show that contrary to classical systems consolidation theories, hippocampal ripples orchestrate recall of both autobiographical and semantic memories. Similarity of ripple patterns furthermore suggests a semantization process as autobiographical memories age.

Memory formation is dynamic in nature, and acquisition of new information is often influenced by previous experiences. Memories sharing certain attributes are known to interact so that retrieval of one increases the likelihood of retrieving the other, raising the possibility that related memories are organized into associative mnemonic structures of interconnected representations. Although the formation

Aggregation of RNA-binding proteins (RBPs) is a pathological hallmark of neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In these diseases, TDP-43 and FUS RBPs are depleted from the nuclear compartment, where they are normally localized, and found within cytoplasmic inclusions in degenerating regions of affected individuals’ postmortem tissue

Although sex dimorphism is increasingly recognized as an important factor in pain, female-specific pain signaling is not well studied. Here we report that administration of IL-23 produces mechanical pain (mechanical allodynia) in female but not male mice, and chemotherapy-induced mechanical pain is selectively impaired in female mice lacking Il23 or Il23r. IL-23-induced pain is promoted by estrogen

The medial temporal lobe (MTL) supports a constellation of memory-related behaviors. Its involvement in perceptual processing, however, has been subject to enduring debate. This debate centers on perirhinal cortex (PRC), an MTL structure at the apex of the ventral visual stream (VVS). Here we leverage a deep learning framework that approximates visual behaviors supported by the VVS (i.e., lacking PRC)

Hippocampal ripples are prominent synchronization events generated by hippocampal neuronal assemblies. To date, ripples have been primarily associated with navigational memory in rodents and short-term episodic recollections in humans. Here, we uncover different profiles of ripple activity in the human hippocampus during the retrieval of recent and remote autobiographical events and semantic facts

Many studies have shown that the excitation and inhibition received by cortical neurons remain roughly balanced across many conditions. A key question for understanding the dynamical regime of cortex is the nature of this balancing. Theorists have shown that network dynamics can yield systematic cancellation of most of a neuron’s excitatory input by inhibition. We review a wide range of evidence pointing

The COVID-19 pandemic has posed major challenges for diversity, equity, and inclusion (DEI) efforts in research and academia. As Chairs of the ALBA Network, we reflect on how the pandemic has exacerbated, and also shone a spotlight on, inequalities in science and society.

The brain has a remarkable but underappreciated capacity to limit memory formation and expression. The term “memory suppressor gene” was coined in 1998 as an attempt to explain emerging reports that some genes appeared to limit memory. At that time, only a handful of memory suppressor genes were known, and they were understood to work by limiting cAMP-dependent consolidation. In the intervening decades

The COVID-19 pandemic has had a profound impact on neuroscientists, including those involved in translational research. In this NeuroView, we discuss the positive and negative impacts of the pandemic on preclinical research and clinical studies in humans.

A major shift is happening within neurophysiology: a population doctrine is drawing level with the single-neuron doctrine that has long dominated the field. Population-level ideas have so far had their greatest impact in motor neuroscience, but they hold great promise for resolving open questions in cognition as well. Here, we codify the population doctrine and survey recent work that leverages this

The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals and is entrained by environmental light. However, the molecular basis of the response of the SCN to light is not fully understood. We used RNA/chromatin immunoprecipitation/single-nucleus sequencing with circadian behavioral assays to identify mouse SCN cell types and explore their responses to light. We identified three

Itch is a discrete and irritating sensation tightly coupled to a drive to scratch. Acute scratching developed evolutionarily as an adaptive defense against skin irritants, pathogens, or parasites. In contrast, the itch-scratch cycle in chronic itch is harmful, inducing escalating itch and skin damage. Clinically and preclinically, scratching incidence is currently evaluated as a unidimensional motor

Psilocybin has emerged as a potentially rapidly acting antidepressant with enduring actions. In this issue of Neuron, Shao et al. (2021) show that psilocybin quickly induces dendritic spine formation in cortical layer V pyramidal neurons. These results provide a potential cellular substrate for psilocybin’s therapeutic actions.

How individual neurons influence epileptic networks remains an open question. In this issue of Neuron, Hadjiabadi et al. (2021) use data-driven, computational models to predict the presence of “superhubs”: highly connected neurons that drive network activity through feedforward motifs.

Inflammation during critical windows of development contributes to behavioral affect later in life. In this of Neuron, Cao et al. (2021) demonstrate a novel mechanism through which early life Tlr4-dependent inflammation in microglia permanently alters neuronal function and leaves male mice susceptible to stress-induced depressive-like behaviors.

In this issue of Neuron, Nguyen and colleagues (Nguyen et al., 2021) investigate nicotine’s effects on diverse midbrain dopamine neurons. Their findings provide new understanding of the functional role of ventral tegmental area (VTA) dopamine neurons and reveal topographically distinct, pathway-specific, and opposite dopaminergic responses to nicotine that likely mediate reward and anxiety, respectively

Establishing a causal link between neural function and behavioral output has remained a challenging problem. Commonly used perturbation techniques enable unprecedented control over intrinsic activity patterns and can effectively identify crucial circuit elements important for specific behaviors. However, these approaches may severely disrupt activity, precluding an investigation into the behavioral

Developing sensory circuits exhibit different patterns of spontaneous activity, patterns that are related to the construction and refinement of functional networks. During the development of different sensory modalities, spontaneous activity originates in the immature peripheral sensory structures and in the higher-order central structures, such as the thalamus and cortex. Certainly, the perinatal