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Learning new associations that reappraise the behavioral significance of previously irrelevant cues requires gamma-frequency synchronization between parvalbumin interneurons in the left and right prefrontal cortex.
Shen et al. report that prolonged obesity is associated with cerebrovascular dysfunction and Tak1 activation in brainstem microglia. Pharmacological inhibition or genetic depletion of Tak1 restores cerebrovascular function in obese mice.
Precisely timed motor learning promotes remyelination in the motor cortex by enhancing oligodendrogenesis and stimulating mature oligodendrocytes to generate new myelin, presenting mature oligodendrocytes as new targets in remyelinating therapies.
Hua and Chen et al. show that general anesthesia activates a distinct population of central amygdala neurons and that these neurons can potently suppress pain responses through their widespread projections to many pain-processing centers in the brain.
Medulloblastomas lacking p53 do not express surface class I major histocompatibility complex (MHC-I) and are resistant to immune rejection. Tumor necrosis factor rescues MHC-I expression and synergizes with immune checkpoint inhibitors to promote rejection.
Cregg et al. find that a specific population of brainstem neurons act to control left–right turning of locomotor movements in mammals through distinct axial- and limb-based mechanisms. This turning pathway is the dominant system for natural directional movements.
The authors establish the claustrum-Cre transgenic mouse line and demonstrate that the claustrum orchestrates cortical slow-wave activity by synchronously driving the inhibitory interneurons in widespread cortical areas.
Marshall et al. show that regions of the genome adopt a noncanonical Z-DNA state in the prefrontal cortex in response to fear learning and that binding of Adar1 reduces Z-DNA during extinction learning, which is required for memory flexibility.
Using fNIRS hyperscanning in three-versus-three-person intergroup competitions, this study shows that in-group bonding and within-group synchronization of reduced dorsolateral prefrontal activity escalate intergroup conflict.
The authors describe a thalamic population, innervated by multimodal brainstem inputs, that forms a CS–US association prior to the lateral amygdala. Its fast and plastic signal defines an amygdala activity pattern necessary for adaptive fear learning.
Flanigan et al. show that activation of inhibitory neurons in the lateral habenula by the neuropeptide orexin (hypocretin) promotes both inter-male aggression and conditioned place preference for contexts associated with winning aggressive contests.
The most common genetic cause of ALS and frontal temporal dementia—hexanucleotide repeat expansion in C9orf72—is shown to provoke disease via synergy of gain of toxicity(ies) from repeat-encoded RNAs/dipeptide repeat proteins and reduction in the C9ORF72 protein.
Hippocampal neurons track events as abstract units of episodic experience. These event representations can be transferred between different experiences and are separately manipulable from hippocampal representations of continuous changes in space.
Kaplan et al. characterize the physiological properties of cells in the primate ventral pallidum. They employ a reinforcement learning model to demonstrate that the different neuronal populations play distinct roles in the basal ganglia network.
Eschbach, Fushiki et al. combine synaptic-resolution circuit mapping, functional analyses and modeling to reveal circuit motifs that regulate dopaminergic neuron activity and may increase associative learning task performance and flexibility.
Jaffe et al. profile the granule cell layer of the human hippocampus and find unique molecular associations for aging and genetic variation, as well as diagnosis with schizophrenia and its genetic risk, that were previously undiscovered in homogenate tissue.
A new spatial transcriptomic approach reveals astrocyte heterogeneity across layers of the mammalian cerebral cortex. Astrocytes diversify into superficial-, mid- and deep-layer subtypes distinct from neuronal laminae, yet instructed by neuronal cues.
Mohammad et al. show that prenatal alcohol exposure increases Kcnn2 activity in the mouse cerebral cortex. Blockade of Kcnn2 improves learning deficits in a mouse model of fetal alcohol spectrum disorders.
Chen, Deister et al. show that Shank3B-knockout mice display hypersensitivity to tactile sensory stimulation and that dysfunction of interneurons in somatosensory cortex contributes to the sensory hyper-reactivity in this mouse model of autism.
Zhou et al. unveil a novel role for activated microglia and macrophages during wound healing after CNS injury. Microglia promote corralling and form a protective barrier at the injury penumbra via the axon guidance receptor Plexin-B2.
Dal Monte et al. investigate neuronal synchrony between the primate amygdala and the anterior cingulate gyrus during social decision-making. Highly specialized coordination between these areas promotes prosocial, compared to antisocial, decisions.
Prior stressful experience affects subsequent behavior even in different situations. Daviu et al. demonstrate that CRHPVN neurons encode stress controllability and contribute to shifts between active and passive innate defensive strategies.
Alpha-synuclein fibrils can disrupt the enteric nervous system, which is mitigated by peripheral GBA1 gene transfer via systemic AAVs. Aging increases susceptibility to α-synuclein pathology progression from the gut to the brain.
Rodriguez et al. define a native role for RAN translation and CGG repeats in regulating mGluR-dependent fragile X protein (FMRP) synthesis. RAN-blocking antisense oligonucleotides increase FMRP and improve survival of neurons from patients with repeat expansions.
Oligodendrocyte precursor cells divide or differentiate in response to external stimuli to control their numbers and to form new myelin. Using zebrafish, we show that these two functions are accomplished by distinct subgroups of cells.
Fear learning induces myelin formation. In the absence of new myelination, remote fear memory and neurophysiology of fear memory circuits are impaired. Conversely, administration of the pro-myelinating drug clemastine enhances remote fear memory.
The authors establish inducible Cxcr4-CreER-based fate mapping as a universal means to identify bone-marrow-derived myeloid cells in the injured brain and demonstrate that Cxcr4 deficiency affects the innate immune response and outcome after stroke.
Microglia in the aging hippocampus accumulate lipid droplets, and are functionally impaired and inflamed. Lipid droplet formation in microglia is regulated by genes linked to neurodegeneration such as progranulin.
High concentrations of sodium are normally unpalatable. This study shows a neural population in the brainstem that suppresses appetite for sodium. Reducing the activity of these neurons can drive ingestion of high concentrations of sodium.
The authors measure evoked activity and perform dense reconstruction of the olfactory bulb wiring diagram in a zebrafish larva, uncovering a mechanism for whitening, a computation that decorrelates activity for pattern classification by memory networks.
Rees et al. show that de novo mutations in the gene SLC6A1, and more broadly across evolutionary constrained genes and genes implicated in neurodevelopmental disorders, increase the risk for developing schizophrenia.
Gao et al. provide evidence that two major classes of neurons exist in the paraventricular thalamus. One of these, termed type II PVT neurons, belongs to a previously ignored cell population that relays arousal information to the infralimbic cortex.
In this study of protein-coding de novo mutations in schizophrenia, researchers found only a small contribution toward overall risk, coming predominantly from genes under negative selection and highly expressed in the brain.
In mice that have undergone Pavlovian reward conditioning, dopaminergic neurons regulate conditioned movements in a temporally restricted manner, consistent with a primary contribution to associative learning rather than online movement generation.
Munn et al. provide evidence that medial entorhinal speed signals scale to reflect the geometry of the environment, whereas entorhinal head direction signals reflect learned information about the geometric symmetry of the environment.
Shuman et al. report that epileptic mice harbor desynchronized hippocampal interneuron activity and unstable spatial representations, revealing that precise intrahippocampal synchronization is critical for spatial coding.
Yoo and colleagues find that while pursuing virtual prey, monkeys predict the prey’s upcoming movements, and neurons in the dorsal anterior cingulate cortex tracked prey position, velocity and acceleration to facilitate these predictions.
Gallego, Perich et al. report that latent dynamics in the neural manifold across three cortical areas are stable throughout years of consistent behavior. The authors posit that these dynamics are fundamental building blocks of learned behavior.
Although Bayesian models provide good accounts of perceptual decisions, it is unclear how their components are represented in the brain. This paper addresses this question by showing that uncertainty decoded from visual cortex helps predict behavior.
Gulli et al. record neurons in the monkey hippocampus during multiple tasks in a virtual reality environment and find that spatial coding is task-dependent. Their analyses reveal rich nonspatial sensory and mnemonic coding of task-related features.
Kappes et al. report a new confirmation bias mechanism. When faced with disagreement, a reduction in the neural sensitivity to the confidence of others is observed leading to a subsequent failure to use others’ confidence to alter one’s own.
Scheggia et al. show that a specific subpopulation of cortical neurons expressing somatostatin in the prefrontal cortex has a primary role in orchestrating the ability of mice to discriminate positive and negative affective states in others.
Bahl and Engert show that larval zebrafish can temporally integrate sensory information. The authors then use brain-wide functional imaging to search for, characterize and model brain areas that are well-suited to implement the underlying processes.
Cocaine-generated silent synapses dictate the encoding, consolidation, retrieval-induced destabilization and reconsolidation of cocaine memories, and these syapses can be targeted to reduce drug seeking and relapse.
Bonnen et al. find that representations of 3D motion in primate cortical neurons have an unexpected structure that is shaped by the projection of the world onto the retinae. They demonstrate a link between this structure and human perceptual errors.