News & Comment

  • Obituary |

    On April 13, the neuroscience community lost a remarkable scientist and true humanitarian. Paul Greengard, co-recipient of the Nobel Prize in Physiology or Medicine in 2000, Vincent Astor Professor and head of the Laboratory of Molecular and Cellular Neuroscience at the Rockefeller University in New York City, died of an apparent heart attack at age 93. Paul will be remembered for his seminal contributions to neuroscience, for pioneering the field of neuronal signal transduction and for training hundreds of neuroscientists. For anyone who knew Paul it will come as no surprise that up until a few hours before his death, Paul was doing what he liked the best: working on a scientific manuscript.

    • Helen S. Bateup
    • , Myriam Heiman
    •  & Anne Schaefer
  • News & Views |

    The creation of a murine Cre driver specific to CNS capillary pericytes has opened a major bottleneck in brain microvascular research. Using this tool, pericyte loss in the adult brain is shown to induce neuronal loss due to concurrent microcirculatory failure and depletion of the protective trophic factor pleiotrophin.

    • Andrée-Anne Berthiaume
    •  & Andy Y. Shih
  • News & Views |

    Shahmoradian and colleagues report that the structure of Lewy bodies in Parkinson’s disease consists of α-synuclein and lipid vesicle clusters instead of the long-assumed amyloid fibril core. This finding has implications for our understanding of the underlying pathogenesis of synucleinopathies.

    • Tim Bartels
  • News & Views |

    A new study by Owen et al. shows that widely used optogenetic light delivery can heat brain tissue and produce changes in neural activity and behavior in the absence of opsins. How will this finding influence experimental design in the optical age of neuroscience?

    • Daniel F. Cardozo Pinto
    •  & Stephan Lammel
  • News & Views |

    Selecting the most rewarding action and performing it accurately are two separable brain functions that are thought to rely upon different neural systems. New evidence suggests that the cerebellum could learn to do both.

    • Javier F. Medina
  • News & Views |

    How to know when to hunt or when to lay low? Surprisingly, new research shows that activity in the medial zona incerta specifically initiates predation in the mouse. The medial zona incerta integrates visual motion and tactile stimulation sent from the intermediate superior colliculus to motivate hunting.

    • Nicole Procacci
    •  & Jennifer L. Hoy
  • News & Views |

    The CNS harbors distinct subsets of macrophages, including parenchymal microglia and macrophages residing at border regions (for example, meninges and the choroid plexus). In this issue of Nature Neuroscience, Van Hove and colleagues elegantly demonstrate the diversity and dynamics of non-parenchymal macrophages and identify a unique microglial subtype within the choroid plexus.

    • Sebastian G. Utz
    •  & Melanie Greter
  • News & Views |

    Using light-activated ion channels to stimulate sensory and motivational pathways, Vetere and colleagues constructed fully artificial memories in mice. Mice preferred or avoided an odor they had never smelled before, depending on the pattern of stimulation.

    • Mark G. Baxter
    •  & Nicholas A. Upright
  • News & Views |

    DNA damage or cellular stresses can induce senescence, and increased senescence with aging contributes to age-associated tissue damage, inflammation and disease. Zheng and colleagues report increased senescent oligodendrocyte progenitor cells around amyloid plaques. Therapeutically eliminating these senescent cells may influence the onset and progression of Alzheimer’s disease pathology.

    • David Holtzman
    •  & Jason Ulrich
  • News & Views |

    Robust conclusions require rigorous statistics. In 2009 a seminal paper described the dangers and prevalence of double-dipping in neuroscience. Ten years on, I consider progress toward statistical rigor in neuroimaging.

    • Katherine S. Button
  • News & Views |

    A new study reveals an unexpected mechanism underlying behavioral abnormalities in the neurodevelopmental disorder Williams syndrome. A deficit in myelination, resulting from the deletion of a Williams syndrome-associated gene in forebrain excitatory neurons, causes hypersociability by impairing action potential conduction. Accordingly, rescuing myelination or conduction normalizes this behavior.

    • Lindsay A. Osso
    •  & Jonah R. Chan
  • News & Views |

    Noninvasive delivery of alternating electrical currents to temporal and prefrontal brain regions improves working memory and reverses age-related changes in brain dynamics in the elderly, report Reinhart and Nguyen in this issue of Nature Neuroscience. They also report a similar effect in young adults with poor working memory performance.

    • Romain Quentin
    •  & Leonardo G. Cohen
  • News & Views |

    The ventrolateral and medial orbitofrontal cortices are involved in selecting actions based on the value of expected outcomes. Malvaez and colleagues reveal that these brain regions are specialized in value encoding (ventrolateral orbitofrontal cortices) versus value memory retrieval (medial orbitofrontal cortices) and that they interact with the basolateral amygdala to orchestrate goal-oriented reward-seeking.

    • Shannon L. Gourley
  • News & Views |

    When choosing whether to act altruistically, people may compare the current option to an idiosyncratic ideal. Prosocial individuals seem to represent deviations from that ideal in the amygdala, but selfish individuals do not. Oxytocin administration makes selfish individuals look more like prosocial individuals, behaviorally and neurally.

    • Ian D. Roberts
    • , Yi Yang Teoh
    •  & Cendri A. Hutcherson
  • News & Views |

    The cell of origin for malignant brain tumors remains uncertain, but de-differentiation from mature cells in the CNS has always been considered a strong possibility. In this issue of Nature Neuroscience, Alcantara Llaguno and colleagues report that differentiated neurons resist transformation by glioblastoma-associated mutations, pointing to neural stem cells or immature progenitors as the most likely cells of origin for these tumors, rather than cells of a relatively mature neuronal lineage.

    • Peter B. Dirks
  • News & Views |

    Astrocytes are emerging as causal or modulating factors in diverse neurological disorders. Two papers published in Nature Neuroscience in 2007 revealed astrocytes as causally contributing to motor neuron loss in amyotrophic lateral sclerosis, thereby challenging the longstanding neuron-centric view of neurodegenerative disease.

    • Shane A. Liddelow
    •  & Michael V. Sofroniew
  • News & Views |

    In this issue of Nature Neuroscience, Kim and colleagues report that corticotropin-releasing factor neurons in the paraventricular nucleus, known essential regulators of the neuroendocrine axis, encode the valence of environmental stimuli through a bidirectional strategy and modulate animals’ immediate behavioral responses.

    • Rui Lin
    • , Ting Yan
    •  & Minmin Luo
  • News & Views |

    Disproportionate reactions to unexpected stimuli and greater attention to perceived threat are cardinal symptoms of post-traumatic stress disorder. Computational psychiatry helps explain how these responses develop and result from abnormalities in learning and prediction during and after traumatic events.

    • Peggy Seriès
  • News & Views |

    Excessive synapse elimination during adolescence and early adulthood has long been hypothesized to underpin the emergence of schizophrenia. A new study reports that induced microglia-like cells derived from schizophrenia patients display increased synapse engulfment, which may be partly mediated by a genetic schizophrenia-risk variant.

    • Meiyan Wang
    • , Lei Zhang
    •  & Fred H. Gage
  • News & Views |

    Geneticists are pushing for ever-greater sample sizes to gain insight into the genetic variation that contributes to psychiatric disorders. Two new genome-wide association studies leverage this approach to provide broad, population-level perspectives on the genetic basis for major depressive disorder and the shared genetic risk that underlies multiple disorders.

    • Lea Karatheodoris Davis
  • News & Views |

    Variability is a ubiquitous aspect of neural recordings. In an influential paper, Churchland et al. (2010) compiled data from many cortical areas to demonstrate that variability generally decreases upon presentation of a stimulus. What are the implications of this finding?

    • Adrienne L. Fairhall
  • News & Views |

    Experience unfolds continuously in time, but we remember discrete sequences of events. In this issue of Nature Neuroscience, Montchal et al. describe brain activity patterns that predict how well people remember precisely when recent events occurred. Converging evidence suggests that homologous neural machinery structures temporal representations in rats and people.

    • Matthew L. Shapiro
  • News & Views |

    In 2008, Vyazovskiy et al. published a seminal study demonstrating that sleep induces a widespread downscaling of synapses that counters the synaptic upscaling that occurred during prior wakefulness. The study laid the groundwork for current research into the ‘where’ and ‘when’ of homeostatic neuronal network regulation during sleep.

    • Niels Niethard
    •  & Jan Born
  • News & Views |

    TDP-43 forms cytoplasmic aggregates in degenerating neurons of frontotemporal dementia (FTD) patients. Laferrière et al. now establish that TDP-43 assemblies from distinct FTD subtypes have different structures, neurotoxicities, and seeding activities, which correlate with FTD severity. Thus, distinct pathological TDP-43 assemblies akin to prion strains might underpin distinct FTD subtypes.

    • Edward M. Barbieri
    •  & James Shorter
  • News & Views |

    In 2010, Johnson and Kenny provided conclusive evidence that extended access to a Western-style diet promotes addictive-like behavior in rats by downregulating D2 receptors while promoting obesity. This focused attention on the parallels between drug addiction and overeating and fueled a decade of food addiction research.

    • Alexandra G. DiFeliceantonio
    •  & Dana M. Small
  • News & Views |

    The locus coeruleus is known to be an essential source of neuromodulation that influences sensory processing, including the enhancement of feature selectivity associated with attentional focus. A new study shows that the primary sensory thalamus encompasses one circuit that underlies this enhancement.

    • Tingting Zhou
    •  & Michael M Halassa
  • News & Views |

    Landmark papers in 2005 and 2009 provided the first evidence of links between development, training, and white-matter plasticity in humans, contributing to a shift in our understanding of brain wiring that has inspired fundamental research into the role of genes, the environment, and the mechanisms underlying training-related plasticity.

    • Christopher J. Steele
    •  & Robert J. Zatorre
  • News & Views |

    In an unfamiliar situation, animals display variable choice behavior. Based on computational modeling and empirical data, a new study suggests that the variability in decision-making across individuals is driven by differences in internal neural dynamics in the medial frontal cortex.

    • Huriye Atilgan
    •  & Alex C. Kwan
  • News & Views |

    The combination of spinal epidural stimulation and physical therapy is restoring walking function to people with spinal cord injury. With intensive rehabilitation, some participants are able to walk in their communities during stimulation and even regain control over previously paralyzed movement in the absence of stimulation.

    • Chet Moritz
  • News & Views |

    Two recent studies have expanded our understanding of the circuits controlling urination: one described a projection from brainstem to spinal cord that relaxes the urethral sphincter, and the other revealed a subpopulation of brainstem-projecting layer 5 pyramidal neurons in primary motor cortex that direct the initiation of urination.

    • Zheyi Ni
    •  & Hailan Hu
  • News & Views |

    What you choose depends on what information your brain considers and what it neglects when computing the value of actions. An early theory used this insight for a computational account of habits versus deliberation. It has ultimately helped uncover how choice in the brain goes beyond such simple dichotomies.

    • Nathaniel D. Daw
  • News & Views |

    A new theory derives the sequential nature of hippocampal replay from first principles and, moreover, predicts the specific patterns of replay that are actually observed in multiple different experiments.

    • John Widloski
    •  & David J. Foster
  • News & Views |

    In this issue of Nature Neuroscience, Menegas et al. demonstrate a role for midbrain dopamine neurons projecting to the tail of the striatum in encoding stimulus novelty and threat avoidance. From this study emerges a model whereby distinct dopaminergic projections to striatum influence behavior along at least two axes, one representing value and one representing threat.

    • Cody A. Siciliano
    • , Fergil Mills
    •  & Kay M. Tye
  • News & Views |

    While the role of protein synthesis in synaptic plasticity and memory is well-established, protein degradation processes have been less studied. A seminal 2003 Nature Neuroscience paper showed that ubiquitin-dependent degradation of synaptic proteins is engaged during activity-regulated synaptic remodeling.

    • Jason D. Shepherd
  • News & Views |

    How we value our own rewards depends on what others have. A new study shows that neurons in the medial prefrontal cortex selectively monitor the value of rewards received by oneself or by another individual, whereas midbrain dopaminergic neurons integrate these values to generate social subjective reward values.

    • Olga Dal Monte
    • , Siqi Fan
    •  & Steve W. C. Chang
  • News & Views |

    The surge in single-cell and single-nucleus RNA-sequencing has raised the question of the value of bulk tissue transcriptomics. Kelley et al. describe an analysis framework by which existing bulk transcriptomic data can be reanalyzed using cell-type-specific data to yield insights into cell-type variation across brain regions and diseases.

    • Vilas Menon
  • News & Views |

    Twenty years ago, 2 studies showed that behavioral experience affects proliferation & survival of newborn neurons in adult hippocampus, suggesting adult neurogenesis as a form of experience-dependent neuroplasticity relevant to memory, emotion, & mental health.

    • Michael R. Drew
    •  & Christine A. Denny
  • News & Views |

    A study has found that young male mice with a mutation of the autism-associated gene Chd8 show abnormal behaviors and elevated neuronal activation in several brain areas under stressful conditions, while female mice with the same mutation have reduced baseline neuronal activity, which may protect them from developing these abnormal phenotypes.

    • Laura C. Andreae
    •  & M. Albert Basson
  • News & Views |

    A deep-learning-based software package called DeepLabCut rapidly and easily enables video-based motion tracking in any animal species. Such tracking technology is bound to revolutionize movement science and behavioral tracking in the laboratory and is also poised to find many applications in the real world.

    • Kunlin Wei
    •  & Konrad Paul Kording
  • News & Views |

    Phenotypic diversity confers the benefits of adaptation to an evolving species. Random perturbations in our genetic structure may result in new functions required for some change in our environment, and we can survive outside of our happy niche for generations. But where are the limits on this sort of diversity?

    • Rosalyn J. Moran
  • News & Views |

    Heterogeneity of function in microglia from different brain regions is suspected but largely unknown. This paper identifies the epigenetic mechanism underlying differential phagocytic activity of microglia in discrete brain regions and examines the consequences of inducing an appetite not commensurate with the level of cell death in the region in which they reside.

    • Staci D. Bilbo
  • News & Views |

    In the 20th century we thought the brain extracted knowledge from sensations. The 21st century witnessed a ‘strange inversion’, in which the brain became an organ of inference, actively constructing explanations for what’s going on ‘out there’, beyond its sensory epithelia. One paper played a key role in this paradigm shift.

    • Karl Friston
  • News & Views |

    Protein kinases are key regulators of excitatory synapse plasticity. In this issue, using novel optical reporters of protein kinase C (PKC) activity, Colgan et al. identify PKCα as critical for integrating NMDA receptor and neurotrophin signaling to control dendritic spine structural plasticity, synaptic potentiation, and learning and memory.

    • Mark L. Dell’Acqua
    •  & Kevin M. Woolfrey
  • News & Views |

    Alzheimer’s disease (AD) research is hampered by a lack of models that recapitulate all key disease features. Park et al. introduce a microfluidic device containing a 3D culture of human neurons, astrocytes, and microglia that develop AD-like pathology, revealing a potentially important inflammatory mechanism of neurodegeneration.

    • Christopher M. Henstridge
    •  & Tara L. Spires-Jones
  • News & Views |

    Often overlooked, the paraventricular nucleus of the thalamus is a stress-sensitive region in the midline thalamus essential for stress-induced adaptations. Using cutting edge in vivo monitoring approaches, Beas, Wright et al. identify a circuit by which stress disinhibits the midline thalamus through dopaminergic modulation arising from the locus coeruleus.

    • Kurt M. Fraser
    •  & Patricia H. Janak
  • News & Views |

    The origin of microglia, the resident macrophage population of the CNS, has been a long-standing matter of debate. Here we discuss two seminal studies published in 2007 in Nature Neuroscience that significantly contributed to a better understanding of microglia ontogeny and homeostasis in the adult brain.

    • Florent Ginhoux
    •  & Sonia Garel
  • News & Views |

    New techniques enable simultaneous optogenetic stimulation and calcium imaging from ensembles of tens of neurons in vivo. Improved opsins are localized to the cell body, minimizing spurious activation of the optically unresolvable neuropil. Two-photon light pulses are sculpted in space, time, and wavelength to efficiently target the desired cells.

    • Adam E. Cohen
    •  & Samouil L. Farhi
  • News & Views |

    In 2004, Weaver et al. published evidence in Nature Neuroscience for the lasting epigenetic impact of maternal care within the hippocampus of rat offspring. This conceptual and methodological leap contributed to the evolution of environmental and behavioral epigenetics and continues to inspire challenging questions about genes, environments, and their legacy.

    • Frances A. Champagne
  • News & Views |

    Synaptic connections adapt homeostatically to changes in experience to maintain optimal circuit function. A study demonstrates that different forms of synaptic homeostasis respond to distinct aspects of circuit activity, suggesting that neurons can gauge and adapt to the both the quality and quantity of circuit activity.

    • Kimberly M. Huber