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When co-cultured with activated microglia, iPSC-derived interneurons from individuals with schizophrenia and from healthy controls show defects in metabolic pathways, but only the interneurons from individuals with schizophrenia showed prolonged metabolic deficits.
Peripheral macrophages located along motor axons react differently to neurodegeneration compared to CNS microglia in ALS mice. Modifying peripheral macrophages suppresses proinflammatory microglial responses, shifting them toward neuronal support.
Donegan et al. show that hippocampal CA2 neurons contribute to social memory by encoding social novelty. Abnormal CA2 coding and social memory in a mouse model of the 22q11.2 microdeletion are rescued by blocking elevated CA2 TREK-1 K+ current.
Aoi et al. used a new dimensionality-reduction method to disentangle the contributions of different task variables to neural population activity, which revealed rotational dynamics in monkey PFC during context-dependent decision-making.
Kohro et al. identify a population of astrocytes located in the superficial dorsal horn of adult spinal cord (genetically defined by Hes5) that acts as a gate for locus coeruleus descending noradrenergic control of mechanosensory hypersensitivity.
This work by Tian and colleagues unveils the extraordinarily complex layout of the human subcortex by identifying 27 new functional regions that organize hierarchically across four scales and adapt to changing cognitive demands.
This study demonstrates that basal ganglia functional topography is maintained across and downstream of its output nuclei, and in closed loops. Focal stimulation of distinct striatal subregions induces distinct action, supporting a model of parallel behavioral control.
Kusick et al. capture snapshots of synaptic vesicle docking and fusion using a new time-resolved electron microscopy technique. They find that vesicles are replaced milliseconds after they fuse, which may contribute to short-term synaptic plasticity.
The authors demonstrate that strongly recurrent circuits inferred from neural activity, even with unlimited data from every neuron, are biased. Synapses are inferred between unconnected but correlated neurons. Inference based on non-equilibrium activity may help remedy this.
Han et al. find that, in addition to powerfully exciting Purkinje cells, climbing fibers rapidly suppress firing in nearby Purkinje cells. Current from glutamate receptor activation generates large extracellular signals that inhibit neighboring cells.
Yamamuro et al. show that juvenile social isolation disrupts prefrontal neurons projecting to the paraventricular thalamus and associated prefrontal somatostatin interneurons, and thereby impairs sociability in adulthood.
Babetto et al. demonstrate an axonal injury-induced glycolytic surge in Schwann cells that supplies perturbed axons with glycolytic energy substrates. Disruption of this metabolic coupling of axons and glial cells promotes axonal degeneration.
Parkinson’s disease brain neurons exhibit a widespread epigenetic dysregulation of enhancers that is linked to an upregulation of TET2. Inactivation of TET2 protects against nigral dopaminergic neuronal loss and neuroinflammation.
Neural oscillations, transients and variability are widely observed in sensory cortices. All these features emerge in neural networks optimized for the singular task of representing perceptual uncertainty in the variability of neural responses.
The nervous system is hypothesized to calculate reward prediction errors to estimate reward availability in the environment. The authors quantify a robust prediction error signal in the ventral pallidum derived from recently received rewarding outcomes.
Park et al. demonstrate in tauopathy models that tau disrupts the interaction between neuronal nitric oxide synthase and PSD95, uncoupling glutamatergic synaptic activity from nitric oxide production and dampening the hemodynamic response to activation.
The authors showed that the ‘moment of perception’ is causally related to dendritic activity in subcortically projecting layer 5 pyramidal neurons that project to the higher-order thalamus, superior colliculus and striatum.
Mazzone and Liang-Guallpa et al. demonstrate that consuming high-fat foods rapidly and durably tunes parallel brain circuits to drive intake of a high-fat diet while devaluing a nutritionally balanced, standard diet even under states of intense hunger.
Kol et al. show that the foundation of remote memory is formed during acquisition by the massive recruitment of ACC-projecting CA1 neurons. Remote memory acquisition involves projection-specific effects of astrocytes on CA1-to-ACC neuronal communication.
Charlet, Grinevich et al. show that social touch between female rats activates parvocellular oxytocin neurons; these neurons control social behavior by coordinating the responses of the much larger population of magnocellular oxytocin neurons.
Yamaguchi et al. identify a little-known amygdalar region, the posterior amygdala, as a key node in male mouse social behaviors. Two largely non-overlapping subpopulations in the posterior amygdala form parallel projections to distinct hypothalamic regions to regulate mating and fighting.
Tamaki et al. measured MRS changes in sleeping humans trained on a visual task. During NREM sleep, learning gains were associated with enhanced visual cortical plasticity that was also seen independent of learning. REM sleep stabilized plasticity only after pre-sleep learning.
Giovannoni et al. report that the aryl hydrocarbon receptor (AHR) is a novel host factor exploited by Zika virus and dengue virus to evade the immune response. AHR is a candidate target for the treatment of Zika virus congenital syndrome and dengue fever.
The complement–microglia pathway is a key mediator of synapse elimination in development and disease. Cong et al. show that neurons endogenously express a complement inhibitor, SRPX2, that regulates synapse elimination in development.
Kelly et al. describe two cerebellum–thalamus–mPFC pathways in mice that regulate social and repetitive behavior. PC activation in Rcrus1 and posterior vermis improved social and reduced repetitive behaviors, respectively, in PC-Tsc1 mutant mice.
Most studies of autism spectrum disorder (ASD) have focused on neuronal mechanisms. Here, the authors describe vascular impairments in a mouse model of 16p11.2 deletion syndrome using physiological and genetic approaches to examine endothelial-dependent phenotypes.
Microglia refine the developing CNS by engulfing excess neurons and synapses. Hughes and Appel here show that microglia also prune myelin sheaths in a neuronal activity-regulated manner to sculpt developmental myelination.
Laszlovszky et al. demonstrate the presence of two types of cholinergic neurons that differ in cellular physiology, coupling with cortical oscillations, synchrony within each group, behavior performance correlates and anatomical distribution.
Lovett-Barron et al. register in situ gene expression to cellular-level neural dynamics in behaving zebrafish and find threat-selective populations spanning multiple hypothalamic peptidergic neuron classes, which converge on brainstem defensive action premotor neurons.
Barbosa, Stein et al. show that rather than operating independently, PFC persistent activity and ‘activity-silent’ mechanisms interact dynamically to produce serial effects in working memory, consistent with attractor models with synaptic plasticity.
Using data from top neuroscience journals, this study finds that women-led work tends to be undercited relative to expectations. This imbalance is driven largely by the citation practices of men and is increasing over time as the field diversifies.
Soden et al. use cell-type-specific retrograde tracing to identify neurotransmitter-specific inputs to the ventral tegmental area, uncovering an underappreciated number of GABAergic inputs with diverse innervation patterns and behavioral functions.
Sasaki et al. demonstrate that neurons in the macaque parietal cortex (ventral intraparietal area) flexibly represent object motion in either a head-centered or world-centered reference frame depending on the requirements of the task.
Mice with AD-like pathology and memory impairments surprisingly have memory engrams in their hippocampus. However, interference with novelty-like cells prevents proper recall, erroneously letting mice perceive a previously learned context as novel.
Andreone, Przybyla et al. used induced pluripotent stem cell-derived human microglia to show that TREM2-dependent phagocytosis and lipid metabolism require the Alzheimer’s risk factor PLCγ2, which can also mediate TREM2-independent inflammatory signaling via Toll-like receptors.
Wimmer et al. show that successful recall of an extended episode of experience in humans is associated with temporally compressed replay of neural patterns associated with the memory, and that the direction of replay depends on task goals.
Cellular imaging reveals that visual cue-evoked activity patterns in visual association cortex are reactivated during subsequent quiet waking. Reactivation rates scale with cue salience and predict next-day changes in functional connectivity and behavior.
An et al. discovered a new brain pathway in mice that conveys light signals from the retina to mood-relevant subcortical nuclei under circadian gating and thereby mediates depressive-like behaviors induced by abnormal nighttime light exposure.
A genetic study of problematic alcohol use in 435,563 individuals, including data from the Million Veteran Program, Psychiatric Genomics Consortium and UK Biobank, found many novel risk loci and provided new insights into trait biology.
Assessing residual consciousness in unresponsive patients is a major clinical concern. Gui et al. demonstrate that EEG-based language assessment can objectively characterize states of consciousness and predict outcomes in individual patients.
Place cell responses are strongly modulated by context, allowing the hippocampus to effectively encode different environments. Electrical recordings show that the context-dependent representation of environmental features is present in the CA3 subregion and is inherited by CA1.
This study elucidates how long-range chromatin loops are altered during short- and long-term changes in neural activity, and analyzes the interplay between the 3D genome and the linear epigenome during activity-dependent transcriptional responses.
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.