Review Articles

  • Review Article |

    While we sleep, the brain replays memories of our experiences during the day. In this review, Klinzing et al. provide a concise overview of how the sleeping brain transforms and builds persisting memories through this process.

    • Jens G. Klinzing
    • , Niels Niethard
    •  & Jan Born
  • Review Article |

    Considerations of optimality have served perceptual neuroscience well, but accumulating evidence suggests that optimal goals can be achieved by heuristic means. Theory that embraces this is key to uncovering the neural basis of perceptual behavior.

    • Justin L. Gardner
  • Review Article |

    Knowledge of the role of glial–neuronal interactions in the physiology of food intake and energy metabolism is emerging. This review highlights the role of astrocytes, microglia, and tanycytes in central control of systemic metabolism.

    • Cristina García-Cáceres
    • , Eglantine Balland
    • , Vincent Prevot
    • , Serge Luquet
    • , Stephen C. Woods
    • , Marco Koch
    • , Tamas L. Horvath
    • , Chun-Xia Yi
    • , Julia A. Chowen
    • , Alexei Verkhratsky
    • , Alfonso Araque
    • , Ingo Bechmann
    •  & Matthias H. Tschöp
  • Review Article |

    A satisfactory understanding of how natural stimuli are encoded by neural circuits has remained elusive. Advances in machine learning provide new approaches to this problem by merging constraints imposed by stimulus statistics and behavioral goals.

    • Maxwell H. Turner
    • , Luis Gonzalo Sanchez Giraldo
    • , Odelia Schwartz
    •  & Fred Rieke
  • Review Article |

    Somatic mutations occur after fertilization and are present in only some cells of an individual. Somatic mutations contribute to normal and abnormal brain development, including neurodevelopmental disorders like autism spectrum disorder.

    • Alissa M. D’Gama
    •  & Christopher A. Walsh
  • Review Article |

    Microglia are the sentinels, housekeepers, and defenders of the brain. In this review we consider the immune checkpoints that control microglial functions and discuss how their imbalance and subsequent neuroinflammation leads to neurodegeneration.

    • Suzanne Hickman
    • , Saef Izzy
    • , Pritha Sen
    • , Liza Morsett
    •  & Joseph El Khoury
  • Review Article |

    Older people often have more than one form of neuropathology. The authors describe how insights from the genomic architecture of syndromically defined neurodegenerative diseases can be integrated to inform person-specific trajectories of brain aging.

    • Philip L. De Jager
    • , Hyun-Sik Yang
    •  & David A Bennett
  • Review Article |

    Neurodegenerative diseases cause progressive loss of brain functions associated with aging. Here we review intricate genotype–phenotype relationships, shared pathogenic mechanisms, and emerging therapeutic opportunities and challenges.

    • Li Gan
    • , Mark R. Cookson
    • , Leonard Petrucelli
    •  & Albert R. La Spada
  • Review Article |

    Adequate blood supply and vascular integrity are key to normal brain functioning. Cerebral blood flow and blood–brain barrier disruption contribute to Alzheimer’s disease and other neurodegenerative disorders as reviewed in humans and animal models.

    • Melanie D. Sweeney
    • , Kassandra Kisler
    • , Axel Montagne
    • , Arthur W. Toga
    •  & Berislav V. Zlokovic
  • Review Article |

    The authors review the current state of rodent models for AD, PD, FTD, and ALS. Limitations and utility of current models, issues regarding translatability, and future directions for developing animal models of these human disorders are discussed.

    • Ted M. Dawson
    • , Todd E. Golde
    •  & Clotilde Lagier-Tourenne
  • Review Article |

    Neurodegenerative diseases impact specific cell populations within the brain. However, not all cells within the population are impacted, a phenomenon called selective cellular vulnerability. The molecular basis of this vulnerability is discussed.

    • Hongjun Fu
    • , John Hardy
    •  & Karen E. Duff
  • Review Article |

    The authors review recent work at the intersection of cognitive science, computational neuroscience and artificial intelligence that develops and tests computational models mimicking neural and cognitive function during a wide range of tasks.

    • Nikolaus Kriegeskorte
    •  & Pamela K. Douglas
  • Review Article |

    Polanía, Nitsche and Ruff summarize the state of non-invasive brain stimulation research in humans, discuss some current debates about properties and limitations of these methods, and give recommendations for how these challenges may be addressed.

    • Rafael Polanía
    • , Michael A. Nitsche
    •  & Christian C. Ruff
  • Review Article |

    The authors propose a new framework for the thalamus in cognition. They review findings from rodents and primates, emphasizing thalamic control of functional cortical connectivity, its putative mechanisms and role in flexible construction of task-relevant cortical networks.

    • Michael M. Halassa
    •  & Sabine Kastner
  • Review Article |

    Distinct processing of objects and space has been an organizing principle for studying higher-level vision and medial temporal lobe memory. Here Connor and Knierim discuss instead how spatial information, on both local and global scales, is deeply integrated into the ventral-temporal object-processing pathway in vision and memory.

    • Charles E Connor
    •  & James J Knierim
  • Review Article |

    Synaptic integration is critical for determining how information in the brain is encoded, stored and retrieved. The authors review roles for synaptic integrative mechanisms in the selection, generation and plasticity of spatially modulated firing, and in related temporal codes for representation of space.

    • Christoph Schmidt-Hieber
    •  & Matthew F Nolan
  • Review Article |

    Cognitive maps are internal representations of large-scale navigable spaces. While they have been long studied in rodents, recent work in humans reveals new insights into how cognitive maps are encoded, anchored to environmental landmarks and used to plan routes. Similar neural mechanisms might be used to form ‘maps’ of nonphysical spaces.

    • Russell A Epstein
    • , Eva Zita Patai
    • , Joshua B Julian
    •  & Hugo J Spiers
  • Review Article |

    Hattori et al. review the recent advances in our understanding of the roles of inhibitory neuron subtypes in shaping the activity and plasticity states of neocortical circuits, how neuromodulators control inhibitory neuron subtypes, and the role of inhibitory neuron dysfunction in neurological disorders.

    • Ryoma Hattori
    • , Kishore V Kuchibhotla
    • , Robert C Froemke
    •  & Takaki Komiyama
  • Review Article |

    The consequences of spinal cord injury are often severe and irreversible; cell transplantation has emerged as a potential treatment. In this Review, the authors highlight mechanisms through which cell transplantation is thought to promote functional improvements and the obstacles to making cell transplantation a viable therapy.

    • Peggy Assinck
    • , Greg J Duncan
    • , Brett J Hilton
    • , Jason R Plemel
    •  & Wolfram Tetzlaff
  • Review Article |

    Cognitive activity requires the collective behavior of cortical, thalamic and spinal neurons across large-scale systems of the CNS. This paper provides an illustrated introduction to dynamic models of large-scale brain activity, from the tenets of the underlying theory to challenges, controversies and recent breakthroughs.

    • Michael Breakspear
  • Review Article |

    Network neuroscience tackles the challenge of discovering the principles underlying complex brain function and cognition from an explicitly integrative perspective. Here, the authors discuss emerging trends in network neuroscience, charting a path towards a better understanding of the brain that bridges computation, theory and experiment across spatial scales and species.

    • Danielle S Bassett
    •  & Olaf Sporns
  • Review Article |

    Magnetoencephalography (MEG) tracks the millisecond electrical activity of the brain noninvasively. This review emphasizes MEG's unique assets, especially in terms of imaging and resolving the mechanisms underlying the apparent complexity of polyrhythmic brain dynamics. It also identifies practical challenges and clarifies misconceptions about the technique.

    • Sylvain Baillet
  • Review Article |

    Neuroimaging and pattern recognition are being combined to develop brain models of clinical disorders. Such models yield biomarkers that can be shared and validated across populations, narrowing the gap between neuroscience and clinical applications. The authors summarize 475 translational modeling studies, highlighting challenges and ways to improve biomarker development.

    • Choong-Wan Woo
    • , Luke J Chang
    • , Martin A Lindquist
    •  & Tor D Wager
  • Review Article |

    The study of neuroanatomy using MRI enables key insights into how our brains function, are shaped by genes and environment, and how they change with development, aging and disease. The authors provide an overview of the methods for measuring the brain and also describe key artifacts and confounds

    • Jason P Lerch
    • , André J W van der Kouwe
    • , Armin Raznahan
    • , Tomáš Paus
    • , Heidi Johansen-Berg
    • , Karla L Miller
    • , Stephen M Smith
    • , Bruce Fischl
    •  & Stamatios N Sotiropoulos
  • Review Article |

    Historically, the CNS has been considered immunologically privileged and separated from the peripheral immune system. In this Review, the authors highlight recent advances in our understanding of how the CNS interacts with peripheral immune cells in the context of health and disease.

    • Marco Prinz
    •  & Josef Priller
  • Review Article |

    Neural pathways regulate immune responses and inflammation. Recent research using technological advances in molecular genetics has provided important insights into the functional anatomy and cellular and molecular mechanisms of this regulation. These advances resulted in clinical trials exploring neuromodulation in the treatment of inflammatory and autoimmune disorders.

    • Valentin A Pavlov
    •  & Kevin J Tracey
  • Review Article |

    Recently, robust identification of hundreds of genetic variants associated with risk for neuropsychiatric disease has prompted new challenges in understanding their biological impact within an individual. The authors provide a framework for interpretation of genetic risk variants to uncover disease mechanisms and facilitate therapeutic development.

    • Michael J Gandal
    • , Virpi Leppa
    • , Hyejung Won
    • , Neelroop N Parikshak
    •  & Daniel H Geschwind
  • Review Article |

    Animal models have failed to yield new treatments for psychiatric disorders. Some psychiatric disorders may result from pathology in plasticity mechanisms. Therefore, understanding plasticity mechanisms in model systems may provide insight into the disordered processes in patients.

    • Bruno B Averbeck
    •  & Matthew V Chafee
  • Review Article |

    Autism spectrum disorders are highly heterogeneous and include both idiopathic and syndromic forms. Sztainberg and Zoghbi discuss insights gained from studying syndromic autism spectrum disorders and their potential contribution to our understanding of the molecular pathways critical for normal cognitive and social development, as well as the relevance to idiopathic autism.

    • Yehezkel Sztainberg
    •  & Huda Y Zoghbi
  • Review Article |

    Functional studies of neuronal assemblies that encode memories have progressed dramatically due to recent technological advances. This review shows how a focus on assembly formation and consolidation provides a powerful conceptual framework to relate mechanistic studies of synaptic, neuronal and circuit plasticity to behaviorally relevant aspects of learning and memory.

    • Anthony Holtmaat
    •  & Pico Caroni
  • Review Article |

    Deficits in developmental synaptic pruning are frequently observed in autism. Here the authors demonstrate molecular pathways shared by pruning and long-term depression (LTD), a synaptic memory mechanism in adult brains that is dysregulated in autism. Thus, autism-related pruning deficits may result from the inability to weaken or disconnect inefficient synapses.

    • Claire Piochon
    • , Masanobu Kano
    •  & Christian Hansel
  • Review Article |

    This paper describes an integrated approach for neuroimaging data acquisition, analysis and sharing. Building on methodological advances from the Human Connectome Project (HCP) and elsewhere, the HCP-style paradigm applies to new and existing data sets that meet core requirements and may accelerate progress in understanding the brain in health and disease.

    • Matthew F Glasser
    • , Stephen M Smith
    • , Daniel S Marcus
    • , Jesper L R Andersson
    • , Edward J Auerbach
    • , Timothy E J Behrens
    • , Timothy S Coalson
    • , Michael P Harms
    • , Mark Jenkinson
    • , Steen Moeller
    • , Emma C Robinson
    • , Stamatios N Sotiropoulos
    • , Junqian Xu
    • , Essa Yacoub
    • , Kamil Ugurbil
    •  & David C Van Essen
  • Review Article |

    Genetically encoded indicators of neuronal activity have diversified and improved in performance in recent years, becoming essential tools for neuroscientists. Lin and Schnitzer review indicators for pH, neurotransmitter, voltage and calcium, with an emphasis on quantifying key indicator attributes and relating them to their applications in neuroscience.

    • Michael Z Lin
    •  & Mark J Schnitzer
  • Review Article |

    Extracellular electrophysiology and calcium imaging are powerful methods for recording neuronal populations. Yet both methods are subject to confounds that, if not accounted for, could lead to erroneous scientific conclusions. The authors discuss these confounds, strategies for identifying and ameliorating them, and potential research that could accurately calibrate population recording.

    • Kenneth D Harris
    • , Rodrigo Quian Quiroga
    • , Jeremy Freeman
    •  & Spencer L Smith
  • Review Article |

    Ji et al. review emerging microscopy technologies that enable large-volume imaging of neural circuits. Focusing on two-photon fluorescence microscopy, they explored critical factors that limit imaging speed and restrict image volume, and also discuss three-dimensional imaging methods and their applications in rapid volume imaging of neural activity.

    • Na Ji
    • , Jeremy Freeman
    •  & Spencer L Smith
  • Review Article |

    Although single-cell gene expression profiling has been possible for the past two decades, a number of recent technological advances in microfluidic and sequencing technology have recently made the procedure much easier and less expensive. Awatramani and colleagues discuss the use of single-cell gene expression profiling for classifying neuronal cell types.

    • Jean-Francois Poulin
    • , Bosiljka Tasic
    • , Jens Hjerling-Leffler
    • , Jeffrey M Trimarchi
    •  & Rajeshwar Awatramani
  • Review Article |

    Pericytes are vascular mural cells embedded in the basement membrane of brain microvessels that, in the CNS, are uniquely positioned in the neurovascular unit between endothelial cells, astrocytes and neurons. Here the authors examine the key signaling pathways between pericytes and their neighboring cells regulating CNS functions in health and disease.

    • Melanie D Sweeney
    • , Shiva Ayyadurai
    •  & Berislav V Zlokovic
  • Review Article |

    The neurobiology of social behavior is highly complex and defects are present in several mental illnesses. Here Barak and Feng discuss neurobiological aspects of two neuropsychiatric disorders presenting opposite social behavior abnormalities, autism spectrum disorder and Williams syndrome.

    • Boaz Barak
    •  & Guoping Feng
  • Review Article |

    The prefrontal cortex supports the expression and inhibition of fear- and reward-related behaviors. These dualities are attributable to discrete functional domains making up this brain region, which allow it to stimulate or inhibit behavior depending on an organism's experiences. The authors review evidence that supports, or refutes, this “go/stop” function.

    • Shannon L Gourley
    •  & Jane R Taylor
  • Review Article |

    In this Review, a collaboration of leading experts in amyotrophic lateral sclerosis (ALS) research present the state of the field regarding the use patient-derived induced pluripotent stem cells to generate motor neurons in vitro. Motor neuron characterization, including transcriptomics, molecular markers, neuron function and electrophysiology, are discussed in the context of maturation and disease.

    • Samuel Sances
    • , Lucie I Bruijn
    • , Siddharthan Chandran
    • , Kevin Eggan
    • , Ritchie Ho
    • , Joseph R Klim
    • , Matt R Livesey
    • , Emily Lowry
    • , Jeffrey D Macklis
    • , David Rushton
    • , Cameron Sadegh
    • , Dhruv Sareen
    • , Hynek Wichterle
    • , Su-Chun Zhang
    •  & Clive N Svendsen
  • Review Article |

    What are the challenges associated with storing information over time in the brain? Here the authors explore the computational principles by which biological memory might be built. They develop a high-level view of shared problems and themes in short- and long-term memory and highlight questions for future research.

    • Rishidev Chaudhuri
    •  & Ila Fiete
  • Review Article |

    Despite representing a minority of cortical cells, inhibitory neurons deeply shape cortical responses. Inhibitory currents closely track excitatory currents, opening only brief windows of opportunity for a neuron to fire. This explains the variability of cortical spike trains, but may also, paradoxically, render a spiking network maximally efficient and precise.

    • Sophie Denève
    •  & Christian K Machens