Animals abstract compact representations of a task’s structure, which supports accelerated learning and flexible behavior. Whether and how such abstracted representations may be used to assign credit for inferred, but unobserved, relationships in structured environments are unknown. We develop a hierarchical reversal-learning task and Bayesian learning model to assess the computational and neural mechanisms

Glutamate excitotoxicity during ischemia triggers an intracellular signaling avalanche leading to cell death, yet blocking NMDA receptors directly in human stroke trials failed. In this issue of Neuron, Zong et al. (2022) disrupt downstream NMDAR-TRPM2 coupling to improve stroke outcomes, supporting intracellular NMDAR signaling as an alternate therapeutic target.

In this issue of Neuron, Szabo et al. uncover a unique subtype of interneurons that is highly active during ripples but largely silent during theta oscillations. The study provides exciting new insights into the regulation and propagation of ripples in CA1 and beyond.

Social modulation of pain sensitivity is considered part of the empathic response. In this issue of Neuron, Zhang at al. (2022) uncover the neurobiological basis of observational pain in mice. They report increased synaptic transmission from the insular cortex to the basolateral amygdala and explore genes mediating this effect.

What are the cellular-level structural and functional changes underlying newly adaptive behaviors in the mammalian brain? In this issue of Neuron, Inada et al. (2022) identify the brain-wide connectivity and synaptic plasticity changes of hypothalamic oxytocin+ neurons in male mice contributing to their parental behaviors.

In this issue of Neuron, Bharioke et al. (2022) demonstrate that diverse general anesthetic regimens all reversibly and selectively synchronize spontaneous activity of pyramidal neurons in layer 5 of mouse cortex. We discuss the implications of these findings for the mechanism of consciousness and anesthetic-induced unconsciousness.

How do neurons and networks of neurons interact spatially? Here, we overview recent discoveries revealing how spatial dynamics of spiking and postsynaptic activity efficiently expose and explain fundamental brain and brainstem mechanisms behind detection, perception, learning, and behavior.

The medial frontal cortex and adjacent orbitofrontal cortex have been the focus of investigations of decision-making, behavioral flexibility, and social behavior. We review studies conducted in humans, macaques, and rodents and argue that several regions with different functional roles can be identified in the dorsal anterior cingulate cortex, perigenual anterior cingulate cortex, anterior medial frontal

Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive of clinical pain disorders. Its electrophysiological correlate is “wind-up,” in which dorsal horn spinal neurons increase their response to repeated nociceptor stimulation. To understand the genetic basis of temporal summation, we undertook a GWAS of wind-up

Processing of sensory information depends on the interactions between hierarchically connected neocortical regions, but it remains unclear how the activity in one area causally influences the activity dynamics in another and how rapidly such interactions change with time. Here, we show that the communication between the primary visual cortex (V1) and high-order visual area LM is context-dependent and

Animals adaptively integrate sensation, planning, and action to navigate toward goal locations in ever-changing environments, but the functional organization of cortex supporting these processes remains unclear. We characterized encoding in approximately 90,000 neurons across the mouse posterior cortex during a virtual navigation task with rule switching. The encoding of task and behavioral variables

Scientists around the globe are joining the race to achieve engineering feats to read, write, modulate, and interface with the human brain in a broadening continuum of invasive to non-invasive ways. The expansive implications of neurotechnology for our conception of health, mind, decision-making, and behavior has raised social and ethical considerations that are inextricable from neurotechnological

Wandelt et al. (2022) show that different grasps can be decoded from neural activity in the human supramarginal gyrus (SMG), ventral premotor cortex, and somatosensory cortex during motor imagery and speech, highlighting the attractiveness of higher-level areas such as the SMG for brain-machine interface applications.

The trigeminal ganglia (TG) play a crucial role in migraine pathophysiology. In this issue of Neuron, Yang et al. developed a single-cell atlas profiling the transcriptome and epigenome of mouse and human TG, thus providing a roadmap for therapeutic targeting.

Working memory enables us to maintain relevant past information for future behavior. In this issue of Neuron, Kwak and Curtis (2022) demonstrate that early visual areas do not simply maintain but flexibly recode sensory percepts into mnemonic codes containing goal-relevant information.

In this issue of Neuron, Berners-Lee et al. (2022) reveal how neural dynamics in the hippocampus change after a single experience, offering a candidate mechanism for how hippocampal plasticity supports episodic memory.

Ancestors of macaques and humans separated into distinct lineages 25 million years ago. Despite this long separation, Hogeveen et al. (2022) show, in this issue of Neuron, that they mediate the explore-exploit tradeoff, which must be managed by any agent adapting to a dynamic environment, using similar computational and neural mechanisms.

Animal behavior is shaped by a variety of “internal states”—partially hidden variables that profoundly shape perception, cognition, and action. The neural basis of internal states, such as fear, arousal, hunger, motivation, aggression, and many others, is a prominent focus of research efforts across animal phyla. Internal states can be inferred from changes in behavior, physiology, and neural dynamics

Transcription factors specify the fate and connectivity of developing neurons. We investigate how a lineage-specific transcription factor, Acj6, controls the precise dendrite targeting of Drosophila olfactory projection neurons (PNs) by regulating the expression of cell-surface proteins. Quantitative cell-surface proteomic profiling of wild-type and acj6 mutant PNs in intact developing brains, and

Neurotechnologies raise ethical concerns overlapping with those of other technologies, like artificial intelligence (AI). We discuss how to leverage the experience and lessons learnt by tech companies addressing AI ethics issues to accelerate going from neuroethics principles to scaled neuroethical industry practice.

Functional ultrasound (fUS) is an emerging technique that measures blood flow to report brain activity. In this issue of Neuron, Nunez-Elizalde et al. (2022) use simultaneous electrophysiological and fUS measurements to quantify the relationship between firing and fUS signals in awake mice.

How is the brain so efficient at excluding proteins, drugs, and immune cells from the blood? In this issue of Neuron, Ayloo et al. (2022) find that an extracellular matrix protein secreted by CNS pericytes shuts down endocytic transport in blood brain barrier endothelial cells.

What causes neurons to die in neurodegenerative disease? In this issue of Neuron, Arredondo et al., 2022 report an unexpected culprit that may drive neuronal death in amyotrophic lateral sclerosis—an evolutionarily ancient energy-storage polymer called polyphosphate (polyP).

A balanced and fine-tuned ratio of neuronal excitation and inhibition is a prerequisite for information processing. In this issue of Neuron, He et al. (2022) reveal a causal link between reduced input to local somatostatin-expressing, MeCP2-negative O-LM interneurons in CA1 and long-term memory impairment in a mouse model of Rett syndrome.

Socioemotional behaviors rely on the integration of information across multiple systems in the brain. In this issue of Neuron, Mague et al. (2022) characterize a multi-regional functional network that coordinates positively valenced social interactions in mice.

Inhibitory neurons (INs) consist of distinct subtypes with unique functions. Previous studies on INs mainly focused on single brain regions, and thus it remains unclear whether the modulation of IN subtypes occurs globally across multiple regions. Here, we monitored the activity of different cortical IN subtypes at both macroscale and microscale in mice learning a lever-press task. Learning evoked

The defining evolutionary feature of eukaryotic cells is the emergence of membrane-bound organelles. Compartmentalization allows each organelle to maintain a spatially, physically, and chemically distinct environment, which greatly bolsters individual organelle function. However, the activities of each organelle must be balanced and are interdependent for cellular homeostasis. Therefore, properly regulated

The hippocampus (HPC) and the lateral prefrontal cortex (LPFC) are two cortical areas of the primate brain deemed essential to cognition. Here, we hypothesized that the codes mediating neuronal communication in the HPC and LPFC microcircuits have distinctively evolved to serve plasticity and memory function at different spatiotemporal scales. We used a virtual reality task in which animals selected

The diversification of cell adhesion molecules by alternative splicing is proposed to underlie molecular codes for neuronal wiring. Transcriptomic approaches mapped detailed cell-type-specific mRNA splicing programs. However, it has been hard to probe the synapse-specific localization and function of the resulting protein splice isoforms, or “proteoforms,” in vivo. We here apply a proteoform-centric

Social gaze interaction powerfully shapes interpersonal communication. However, compared with social perception, very little is known about the neuronal underpinnings of real-life social gaze interaction. Here, we studied a large number of neurons spanning four regions in primate prefrontal-amygdala networks and demonstrate robust single-cell foundations of interactive social gaze in the orbitofrontal

Flexible mapping between activity in sensory systems and movement parameters is a hallmark of motor control. This flexibility depends on the continuous comparison of short-term postural dynamics and the longer-term goals of an animal, thereby necessitating neural mechanisms that can operate across multiple timescales. To understand how such body-brain interactions emerge across timescales to control

Animal brains have discrete circadian neurons, but little is known about how they are coordinated to influence and maintain sleep. Here, through a systematic optogenetic screening, we identified a subtype of uncharacterized circadian DN3 neurons that is strongly sleep promoting in Drosophila. These anterior-projecting DN3s (APDN3s) receive signals from DN1 circadian neurons and then output to newly

We make complex decisions using both fast judgments and slower, more deliberative reasoning. For example, during value-based decision-making, animals make rapid value-guided orienting eye movements after stimulus presentation that bias the upcoming decision. The neural mechanisms underlying these processes remain unclear. To address this, we recorded from the caudate nucleus and orbitofrontal cortex

Pediatric brain tumor treatments have a high success rate, but survivors are at risk of cognitive sequelae that impact long-term quality of life. We summarize recent clinical and animal model research addressing pathogenesis or evaluating candidate interventions for treatment-induced cognitive sequelae. Assayed interventions encompass a broad range of approaches, including modifications to radiotherapy

Genetic and environmental factors during development are involved in autism, and in this issue of Neuron Krüttner et al. (2022) find environment may play a more acute role in modulating autism behavior in a Shank3 exon 21 deletion mutant mouse (Shank3ΔC/ΔC). The authors explore the underlying circuit mechanisms in detail.

Active zones are colossal and complex molecular machines that transform electrical signals into rapid neurotransmitter secretion. In this issue of Neuron, Tan et al. (2022) elegantly distill central functions of this synaptic apparatus by tethering a small domain of the scaffold RIM near Ca2+ channels.

Cortical pyramidal neurons receive thousands of synaptic inputs and transform these into action potential output. In this issue of Neuron, Lafourcade et al. (2022) demonstrate that distinct long-range projections to retrosplenial cortex pyramidal neurons are coupled to diverse modes of dendritic integration.

In this issue of Neuron, Widloski and Foster (2022) show that, in a complex maze with changing barrier configurations, rat hippocampal neurons maintain their location-specific firing but learn to generate activity sequences representing possible routes to rewards, that respect the locations of barriers, and to rapidly adapt to barrier reconfiguration.

In this issue of Neuron, Lopez-Rojas et al. (2022) uncover a cortical circuit conveying social information to CA2, a region essential for social memory. Their findings suggest CA2 neurons integrate information from other extrahippocampal circuits to locally compute social novelty.

In a recent issue of Nature, Marek et al. (2022) demonstrate that cross-sectional brain-behavior correlations are often small and unreliable without large samples. This observation pushes human neuroscience toward study designs that either maximize sample sizes to detect small effects or maximize effect sizes using focused investigations.

Retinal ganglion cells (RGCs) are the spiking projection neurons of the eye that encode different features of the visual environment. The circuits providing synaptic input to different RGC types to drive feature selectivity have been studied extensively, but there has been less research aimed at understanding the intrinsic properties and how they impact feature selectivity. We introduce an RGC type

People with Down syndrome (DS) have increased risk of Alzheimer disease (AD), presumably conferred through genetic predispositions arising from trisomy 21. These predispositions necessarily include triplication of the amyloid precursor protein (APP), but also other Ch21 genes that confer risk directly or through interactions with genes on other chromosomes. We discuss evidence that multiple genes on

The ability to sense the environment is essential to survival and is the primary purpose of the somatosensory nervous system. However, despite its highly conserved nature, the sensation of itch has been historically overlooked, and its importance in medicine underappreciated. Herein, we highlight how fundamental discoveries, coupled to rapid successes of new therapeutics, have placed itch biology at

Neural responses to vocalizations are expected to depend on the sensory features of the stimulus. In this issue of Neuron, Jovanovic and colleagues show that call-responsive neurons in the prefrontal cortex of marmosets signal not only the auditory stimulus but also the social-behavioral context.

Communication between the nervous system and immune system is important for regulating immunity in health and disease. Yu et al. (2022) show that neuropeptide Y and its homolog NPF serve as a “language” to facilitate crosstalk between these two systems across species, enabling neurons to downregulate harmful immune responses.

Usage of alternative mRNA 3′ ends has profound functional consequences, particularly in the nervous system. In this issue of Neuron, LaForce et al. (2022) dissect the effect of CLP1 on mRNA 3′ end diversity in motor neuron models of neurodegeneration.