Research

This list contains the 50 most recently published research articles, including advance online publication articles that have not yet been published in a journal issue.

Showing: 1–25 of 50

AOP
  1. Activation of cortical somatostatin interneurons prevents the development of neuropathic pain AOP

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    Using in vivo calcium imaging in a mouse model of neuropathic pain, the authors found a persistent increase in the activity of somatosensory cortex pyramidal neurons following peripheral nerve injury. Repeated pharmacogenetic activation of somatostatin-expressing inhibitory neurons after injury not only corrected this abnormal cortical activity but also prevented the development of chronic pain.

  2. Spatiotemporal profile of postsynaptic interactomes integrates components of complex brain disorders AOP

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    Using large-scale analysis of protein interactions and bioinformatics, Li et al. describe the organization of the core-scaffold machinery of the postsynaptic density and its assembly in protein-interaction networks. The authors show how mutations associated with complex brain disorders are distributed along spatiotemporal protein complexes and modulate their protein interactions.

  3. Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems AOP

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    The authors report two new engineered AAV capsids that efficiently deliver genes throughout the adult central and peripheral nervous systems after intravenous administration. Complementing these capsids is an AAV toolbox that enables cell morphology and genetic manipulation studies of defined neural cell types in transgenic or wild-type animals.

  4. Germline Chd8 haploinsufficiency alters brain development in mouse AOP

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    Strong genetic evidence points to a significant role for heterozygous mutations to general chromatin remodeling factors, such as CHD8, in autism. Gompers et al. combine genomic, neuroanatomical and behavioral approaches to present an initial integrative picture of transcriptional mechanisms and widespread impacts of Chd8 haploinsufficiency across brain development in mice.

  5. Dynamic illumination of spatially restricted or large brain volumes via a single tapered optical fiber AOP

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    The authors demonstrate that optical fibers with tapered tips can homogenously illuminate either elongated brain structures or dynamically selected subregions. Tapered fibers achieve efficient optogenetic stimulation in vivo with minimal tissue damage. In addition, a single fiber can deliver light of multiple wavelengths to independently controlled regions.

  6. Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1 AOP

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    The precise mechanisms that cause human obesity remain unknown. Here the authors illustrate how increased expression of Cadm1, a mediator of synapse assembly, is relevant to weight gain. Reduction of Cadm1 in multiple brain regions promoted weight loss, and these observations provide insight into the neuronal pathways contributing to obesity.

  7. Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains AOP

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    This study characterizes the properties of disease-causing mutations that produce sporadic amino acid replacements in proteins of people with autism and developmental delay. The mutations tend to cluster and reoccur at specific regions important to protein function, highlighting for future follow-up ∼200 candidate genes, many involved in neuronal signaling.

  8. A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease AOP

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    The authors identified a protective genetic allele associated with lower PU.1 (SPI1) expression in myeloid cells by conducting a genome-wide scan of Alzheimer's disease (AD). PU.1 binds the promoters of AD-associated genes (e.g., CD33, MS4A4A & MS4A6A, TYROBP) and modulates their expression, suggesting it may reduce AD risk by regulating myeloid cell gene expression.

  9. Active dendritic integration as a mechanism for robust and precise grid cell firing AOP

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    Combining electrophysiology and computational modeling, the authors show that the dendrites of entorhinal cortex stellate and pyramidal cells are electrically excitable and that this improves the robustness of grid cell firing. The results suggest that active dendrites are critical for spatial navigation, a fundamental computation in the brain.

  10. A TNF–JNK–Axl–ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma AOP

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    Aberrant EGFR signaling is common in glioblastoma. The authors show that inhibiting EGFR leads to increased secretion of TNF and activation of a survival pathway in cancer cells. A combined inhibition of EGFR and TNF signaling inhibits tumor growth in a mouse model, suggesting a new treatment for patients with glioblastoma.

  11. Neural signatures of dynamic stimulus selection in Drosophila AOP

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    Using two-color two-photon calcium imaging, the authors identified transformations of representations across synaptically connected pairs of neurons along a visual pathway to the Drosophila central complex. Neural responses to stimuli in the ipsilateral field are modulated by stimuli in the contralateral field, an effect that depends on past stimulus history.

  12. Sensory integration and neuromodulatory feedback facilitate Drosophila mechanonociceptive behavior AOP

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    Noxious thermal and mechanical stimuli have to be faithfully detected and avoided to ensure survival. In this study, the authors uncover a modality-specific circuit responsible specifically for mechanonociceptive behavior in Drosophila. They show that the escape response to mechanical but not thermal noxious stimuli requires multisensory integration by mechanosensory neurons and neuromodulatory feedback signaling.

  13. Rich cell-type-specific network topology in neocortical microcircuitry AOP

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    To unravel structural regularities in neocortical networks, Gal et al. analyzed a biologically constrained model of a neocortical microcircuit. Using extended graph theory, they found multiple cell-type-specific wiring features, including small-word and rich-club topologies that might contribute to the large repertoire of computations performed by the neocortex.

  14. Cancer-induced anorexia and malaise are mediated by CGRP neurons in the parabrachial nucleus AOP

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    Most cancer patients experience loss of appetite and feelings of illness, which contribute to cancer-related deaths and morbidity. The authors demonstrate that, in mice, activation of a subset of neurons in the parabrachial nucleus mediate cancer-induced anorexia and associated sickness behaviors.

  15. Reinstated episodic context guides sampling-based decisions for reward AOP

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    The authors demonstrate that decisions for reward can have more a complicated dependence on past experiences than previously believed. Previous models describe decisions as influenced by rewards received in similar situations. Here the authors show that experiences that share only incidental features can also reemerge to bias present choices.

  16. The cellular mechanism for water detection in the mammalian taste system AOP

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    The authors find that mammalian acid-sensing taste receptor cells, previously shown to be putative sour taste sensors, also mediate responses to water. Optogenetic activation of this population of cells in thirsty mice induced robust drinking response in the absence of water. This study shows that acid-sensing TRCs contribute to the detection of water in the oral cavity.

  17. Attention-related changes in correlated neuronal activity arise from normalization mechanisms AOP

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    Attention changes correlations between neuronal responses. In this study, Verhoef and Maunsell use multielectrode recordings in monkeys to reveal a link between normalization mechanisms, correlated neuronal activity and attention. The findings show that normalization mechanisms shape response correlations and that these correlations change when attention biases normalization mechanisms.

  18. Flexible information routing by transient synchrony AOP

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    Brain function relies on flexible communication between cortical regions. It has been proposed that changing patterns of oscillatory coherence underlie information routing. However, oscillations in vivo are very irregular. This study shows that short-lived and stochastic oscillatory bursts coordinate across areas to selectively modulate interareal communication.

  19. A cerebellum-like circuit in the auditory system cancels responses to self-generated sounds AOP

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    The authors provide evidence that a cerebellum-like structure at the initial stage of mammalian auditory processing (the dorsal cochlear nucleus) functions to cancel out self-generated sounds. A similar function has been established for cerebellum-like structures in electroreceptive fish, suggesting a conserved function for these structures across vertebrates.

  20. Causal evidence for retina-dependent and -independent visual motion computations in mouse cortex AOP

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    The authors monitored neuronal activity in mouse visual cortex during visual-motion stimulation and perturbed retinal direction selectivity. After perturbation, the proportion of posterior-motion-preferring cortical cells decreased, and their response at higher stimulus speeds was reduced. Thus, functionally distinct, retina-dependent and retina-independent computations of visual motion exist in mouse cortex.

  21. PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1 AOP

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    The authors identify programmed cell death ligand-1 (PD-L1), an immunity suppressor produced by cancer cells, as a new pain inhibitor and a neuromodulator. They report that PD-L1 is produced by melanoma and normal neural tissues and that it inhibits acute and chronic pain. Via activation of PD-1, its receptor, PD-L1 decreases the excitability of nociceptive neurons in mouse and human dorsal root ganglia.

  22. A fluoro-Nissl dye identifies pericytes as distinct vascular mural cells during in vivo brain imaging AOP

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    No techniques exist for the precise identification of vascular pericytes. Here the authors identify and characterize a fluorescent dye that exclusively labels pericytes. Using this tool for intravital imaging of the mouse brain, the authors provide conclusive evidence that these cells are molecularly and functionally distinct from all other brain and vascular cells.

  23. Identification of a motor-to-auditory pathway important for vocal learning AOP

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    Although vocal learning is widely speculated to depend on motor to auditory (i.e., forward) pathways, the neurons that convey forward signals important to vocal learning remain unknown. Here the authors identify neurons that transmit signals from songbird motor to auditory regions and demonstrate their role in vocal learning.