Experiments identify cortical layer specific effects during induced arousal from general anesthesia. In this issue of Neuron, Redinbaugh et al. (2020) find evidence that central lateral thalamic nucleus electrical stimulation reactivates the cortex by restoring deep-layer firing rates and modulating feedforward and feedback connectivity.

Forward genetic screen, typically performed in invertebrates or mammalian cell lines, has been instrumental in discovering genes essential for neural function. In this issue of Neuron, Wertz et al. (2020) demonstrate the first viral-mediated, genome-wide screen to identify neuroprotective genes in wild-type and Huntington’s disease (HD) mouse brains.

Defective nucleocytoplasmic transport contributes to C9-ALS/FTD, but an inventory of proteins that become redistributed has remained elusive. In this issue of Neuron, Ortega et al. (2020) catalog these redistributed proteins and pinpoint nonsense-mediated decay as a therapeutic target for C9-ALS/FTD.

How are head direction signals computed and maintained in neural circuits? In this issue of Neuron, Shiozaki et al. (2020) expand our understanding of the fly “compass” network, revealing context- and experience-dependent changes in the multiplexed encoding of head direction and steering maneuvers.

In this issue of Neuron, Morrens et al. (2020) show that stimulus-evoked dopamine responses are enhanced by novelty and increase the rate at which animals acquire conditioned responses. These results provide a candidate neural mechanism for latent inhibition and illustrate a new role of dopamine signals in learning.

Neurons in neocortical layer 1 (L1) are thought to regulate attentional processes through integration of long-range inputs and disinhibitory effects on the underlying cortex. A new study combines genetically targeted voltage imaging and optogenetics to elucidate the input-output transformations of the L1 network in the mouse somatosensory cortex, revealing unique features of sensory-evoked dynamics

The world faces a climate emergency. Here, we consider the actions that can be taken by neuroscientists to tackle climate change. We encourage neuroscientists to put emissions reductions at the center of their everyday professional activities.

Since the discovery of ocular dominance plasticity, neuroscientists have understood that changes in visual experience during a discrete developmental time, the critical period, trigger robust changes in the visual cortex. State-of-the-art tools used to probe connectivity with cell-type-specific resolution have expanded the understanding of circuit changes underlying experience-dependent plasticity

The habenula complex is appreciated as a critical regulator of motivated and pathological behavioral states via its output to midbrain nuclei. Despite this, transcriptional definition of cell populations that comprise both the medial habenular (MHb) and lateral habenular (LHb) subregions in mammals remain undefined. To resolve this, we performed single-cell transcriptional profiling and highly multiplexed

Postingestive nutrient sensing can induce food preferences. However, much less is known about the ability of postingestive signals to modulate food-seeking behaviors. Here we report a causal connection between postingestive sucrose sensing and vagus-mediated dopamine neuron activity in the ventral tegmental area (VTA), supporting food seeking. The activity of VTA dopamine neurons increases significantly

Autism spectrum disorder (ASD) is more prevalent in males; however, the etiology for this sex bias is not well understood. Many mutations on X-linked cell adhesion molecule NLGN4X result in ASD or intellectual disability. NLGN4X is part of an X-Y pair, with NLGN4Y sharing ∼97% sequence homology. Using biochemistry, electrophysiology, and imaging, we show that NLGN4Y displays severe deficits in maturation

Predictive learning exerts a powerful influence over choice between instrumental actions. Nevertheless, how this learning is encoded in a sufficiently stable manner to influence choices that can occur much later in time is unclear. Here, we report that the basolateral amygdala (BLA) encodes predictive learning and establishes the memory necessary for future choices by driving the accumulation of delta-opioid

Excitation in neural circuits must be carefully controlled by inhibition to regulate information processing and network excitability. During development, cortical inhibitory and excitatory inputs are initially mismatched but become co-tuned or balanced with experience. However, little is known about how excitatory-inhibitory balance is defined at most synapses or about the mechanisms for establishing

Mutations in Shank3 are strongly associated with autism spectrum disorders and neural circuit changes in several brain areas, but the cellular mechanisms that underlie these defects are not understood. Homeostatic forms of plasticity allow central circuits to maintain stable function during experience-dependent development, leading us to ask whether loss of Shank3 might impair homeostatic plasticity

Working memory relies on the dorsolateral prefrontal cortex (dlPFC), where microcircuits of pyramidal neurons enable persistent firing in the absence of sensory input, maintaining information through recurrent excitation. This activity relies on acetylcholine, although the molecular mechanisms for this dependence are not thoroughly understood. This study investigated the role of muscarinic M1 receptors

In this issue of Neuron, Sinha et al. (2020) demonstrate that synaptic organization at rod bipolar cell terminals is regulated by a leucine-rich repeat protein, LRRTM4. LRRTM4 is expressed specifically by rod bipolar cells; eliminating it in mouse retina perturbs the organization of synaptic ribbons and impairs the function of inhibitory synapses.

Noradrenergic cells of the locus coeruleus were associated with aversive learning and arousal. In this issue of Neuron, Kaufman et al. (2020) show that they also shape the spatial map after translocation of reward.

In this issue of Neuron, Corkrum et al. (2020) demonstrate an unexpected role for dopamine D1 receptors on astrocytes located in the nucleus accumbens, a key structure of the brain’s reward system. Activation of these receptors mediates dopamine-evoked depression of excitatory synaptic transmission, which contributes to amphetamine’s psychomotor effects.

By exploiting an arsenal of state-of-the-art imaging and genetic manipulation approaches, in this issue of Neuron, Marcus et al. (2020) reveal that the synapse-specific breakdown of endocannabinoid signaling in the prelimbic prefrontal cortex is a core neurobiological substrate for stress-induced, anxiety-like behaviors.

The neural mechanisms underlying interoception—the sensation of internal physiological states—remain largely unresolved. In this issue of Neuron, Livneh et al. (2020) demonstrate that the insula bridges different timescales of interoception by tracking and predicting thirst and hunger states.

Autophagy is a key cellular degradative pathway, important for neuronal homeostasis and function. Disruption of autophagy is associated with neuronal dysfunction and neurodegeneration. Autophagy is compartmentalized in neurons, with specific stages of the pathway occurring in distinct subcellular compartments. Coordination of these stages drives progression of autophagy and enables clearance of substrates

When individuals learn from observing the behavior of others, they deploy at least two distinct strategies. Choice imitation involves repeating other agents’ previous actions, whereas emulation proceeds from inferring their goals and intentions. Despite the prevalence of observational learning in humans and other social animals, a fundamental question remains unaddressed: how does the brain decide

To take the best actions, we often need to maintain and update beliefs about variables that cannot be directly observed. To understand the principles underlying such belief updates, we need tools to uncover subjects’ belief dynamics from natural behavior. We tested whether eye movements could be used to infer subjects’ beliefs about latent variables using a naturalistic navigation task. Humans and

The balance between excitatory and inhibitory (E and I) synapses is thought to be critical for information processing in neural circuits. However, little is known about the spatial principles of E and I synaptic organization across the entire dendritic tree of mammalian neurons. We developed a new open-source reconstruction platform for mapping the size and spatial distribution of E and I synapses

How does information from seconds earlier affect neocortical responses to new input? We found that when two groups of participants heard the same sentence in a narrative, preceded by different contexts, the neural responses of each group were initially different but gradually fell into alignment. We observed a hierarchical gradient: sensory cortices aligned most quickly, followed by mid-level regions

Neuronal oscillations in the frontal cortex have been hypothesized to play a role in the organization of high-level cognition. Within the orbitofrontal cortex (OFC), there is a prominent oscillation in the theta frequency (4–8 Hz) during reward-guided behavior, but it is unclear whether this oscillation has causal significance. One methodological challenge is that it is difficult to manipulate theta

Dendrite arbor pattern determines the functional characteristics of a neuron. It is founded on primary branch structure, defined through cell intrinsic and transcription-factor-encoded mechanisms. Developing arbors have extensive acentrosomal microtubule dynamics, and here, we report an unexpected role for the atypical actin motor Myo6 in creating primary branch structure by specifying the position

The ability to dynamically change motor outputs, such as stopping an initiated response, is an important aspect of human behavior. A hyperdirect pathway between the inferior frontal gyrus and subthalamic nucleus is hypothesized to mediate movement inhibition, but there is limited evidence for this in humans. We recorded high spatial and temporal resolution field potentials from both the inferior frontal

Voluntary movement initiation involves the modulations of large groups of neurons in the primary motor cortex (M1). Yet similar modulations occur during movement planning when no movement occurs. Here, we show that a sequential spatiotemporal pattern of excitability propagates across M1 prior to the movement initiation in one of two oppositely oriented directions along the rostro-caudal axis. Using

Lipid-processing mechanisms during demyelination are poorly understood. In this issue of Neuron, Nugent et al. (2020) show by cell-specific lipidomics that Trem2 deficiency leads to cholesterol ester (CE) overload in microglia. This is mediated by misregulation of lipid metabolism genes and is rescued by modulating CE synthesis or efflux.

Which elements of the genome endow human brains with the capacity for heightened cognitive abilities? In this issue of Neuron, Namba et al. (2020) find that ARHGAP11B, a human-specific gene, augments cerebral cortex expansion by regulating metabolic pathways in mitochondria.

In this issue of Neuron, Roth et al. (2020) report that the content of GluA1-containing AMPAR at spines and dendrites in vivo in the motor and visual cortex increases proportionally to the learning of a motor task. Visual cortex activity is necessary for increasing AMPAR content and learning in light.

In this issue of Neuron, Stephenson-Jones et al. (2020) dissect the function of the enigmatic ventral pallidum and elegantly demonstrate positive and negative valence encoding in its GABA and glutamate neurons that influence both approach and avoidance behavior via the lateral habenula.

Highly portable, cloud-enabled neuroimaging technologies will fundamentally change neuroimaging research. Instead of participants traveling to the scanner, the scanner will now come to them. Field-based brain imaging research, including populations underrepresented in neuroscience research to date, will enlarge and diversify databases and pave the way for clinical and direct-to-consumer (DTC) applications

We review the central tenets and neuroanatomical basis of the global neuronal workspace (GNW) hypothesis, which attempts to account for the main scientific observations regarding the elementary mechanisms of conscious processing in the human brain. The GNW hypothesis proposes that, in the conscious state, a non-linear network ignition associated with recurrent processing amplifies and sustains a neural

Whether transient or sustained neuronal activity during the delay period underlies working memory (WM) has been debated. Here, we report that transient, but not sustained, delay-period activity in mouse anterior agranular insular cortex (aAIC) plays a dominant role in maintaining WM information during learning of novel olfactory tasks. By optogenetic screening over 12 brain regions, we found that suppressing

Autism is characterized by repetitive behaviors, impaired social interactions, and communication deficits. It is a prevalent neurodevelopmental disorder, and available treatments offer little benefit. Here, we show that genetically reducing the protein tau prevents behavioral signs of autism in two mouse models simulating distinct causes of this condition. Similar to a proportion of people with autism

The activity-dependent rules that govern the wiring of GABAergic interneurons are not well understood. Chandelier cells (ChCs) are a type of GABAergic interneuron that control pyramidal cell output through axo-axonic synapses that target the axon initial segment. In vivo imaging of ChCs during development uncovered a narrow window (P12-P18) over which axons arborized and formed connections. We found

Cognitive capacities afford contingent associations between sensory information and behavioral responses. We studied this problem using an olfactory delayed match to sample task whereby a sample odor specifies the association between a subsequent test odor and rewarding action. Multi-neuron recordings revealed representations of the sample and test odors in olfactory sensory and association cortex

Genes mutated in human neuronal migration disorders encode tubulin proteins and a variety of tubulin-binding and -regulating proteins, but it is very poorly understood how these proteins function together to coordinate migration. Additionally, the way in which regional differences in neocortical migration are controlled is completely unknown. Here we describe a new syndrome with remarkably region-specific

Lissencephaly (LIS), denoting a "smooth brain," is characterized by the absence of normal cerebral convolutions with abnormalities of cortical thickness. Pathogenic variants in over 20 genes are associated with LIS. The majority of posterior predominant LIS is caused by pathogenic variants in LIS1 (also known as PAFAH1B1), although a significant fraction remains without a known genetic etiology. We

Balance between excitation and inhibition (E-I balance) in neural circuits is believed to be tightly regulated. To the contrary, in this issue of Neuron, Bridi et al. (2020) reveal that inverse oscillations of synaptic inhibition and excitation lead to peaks and valleys in E-I balance across the 24 h day.