Volume 21 Issue 6, June 2018

Volume 21 Issue 6

Learning how to learn

Humans and other animals must ‘learn how to learn’, figuring out how to leverage past experiences to learn rapidly in new situations. Every instance of learning therefore reflects a previous history of related learning experiences, as playfully illustrated on the cover. In this issue, Wang and colleagues show how learning to learn may arise from an interplay between the dopaminergic system and prefrontal cortex.

See Wang et al.

Image: DeepMind. Cover Design: Erin Dewalt.

News & Views

  • 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
  • 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

Perspectives

  • Perspective |

    Microglial immune checkpoint mechanisms are signaling pathways that limit immune responsiveness and promote homeostatic activities of micrroglia throughout life, but can interfere with repair mechanisms in disease.

    • Aleksandra Deczkowska
    • , Ido Amit
    •  & Michal Schwartz
  • Perspective |

    In this Perspective, Josh Berke discusses recent developments in the study of dopamine function. He proposes a model that explains how dopamine can serve as both a learning signal and as a critical modulator of motivated decision-making.

    • Joshua D. Berke

Brief Communications

  • Brief Communication |

    Whether MeCP2 competes with linker histone H1 for DNA binding has never been tested in vivo. Ito-Ishida et al. performed ChIP-seq on MeCP2 and Flag-H1.0 in mouse forebrain neurons and reveal that their genomic distributions are largely independent.

    • Aya Ito-Ishida
    • , Hari Krishna Yamalanchili
    • , Yingyao Shao
    • , Steven A. Baker
    • , Laura D. Heckman
    • , Laura A. Lavery
    • , Ji-yoen Kim
    • , Laura M. Lombardi
    • , Yaling Sun
    • , Zhandong Liu
    •  & Huda Y. Zoghbi
  • Brief Communication |

    mTORC1 was posited as required for hippocampal mGluR-LTD at CA1 synapses based on its pharmacological inhibition with rapamycin. Using molecular genetics, the authors show that mTORC2 but not mTORC1 is required for mGluR-LTD and associated behaviors.

    • Ping Jun Zhu
    • , Chien-Ju Chen
    • , Jacqunae Mays
    • , Loredana Stoica
    •  & Mauro Costa-Mattioli
  • Brief Communication |

    The neuropeptide CRH is believed to induce aversive, stress-like behavioral responses. Here the authors describe a distinct population of CRH neurons in the extended amygdala that act to suppress anxiety by positively modulating dopamine release.

    • Nina Dedic
    • , Claudia Kühne
    • , Mira Jakovcevski
    • , Jakob Hartmann
    • , Andreas J. Genewsky
    • , Karina S. Gomes
    • , Elmira Anderzhanova
    • , Max L. Pöhlmann
    • , Simon Chang
    • , Adam Kolarz
    • , Annette M. Vogl
    • , Julien Dine
    • , Michael W. Metzger
    • , Bianca Schmid
    • , Rafael C. Almada
    • , Kerry J. Ressler
    • , Carsten T. Wotjak
    • , Valery Grinevich
    • , Alon Chen
    • , Mathias V. Schmidt
    • , Wolfgang Wurst
    • , Damian Refojo
    •  & Jan M. Deussing

Articles

  • Article |

    The authors constructed and validated a molecular network of the aging human cortex from RNA sequencing data from 478 individuals and identified genes that affect cognitive decline or neuropathology in Alzheimer’s disease.

    • Sara Mostafavi
    • , Chris Gaiteri
    • , Sarah E. Sullivan
    • , Charles C. White
    • , Shinya Tasaki
    • , Jishu Xu
    • , Mariko Taga
    • , Hans-Ulrich Klein
    • , Ellis Patrick
    • , Vitalina Komashko
    • , Cristin McCabe
    • , Robert Smith
    • , Elizabeth M. Bradshaw
    • , David E. Root
    • , Aviv Regev
    • , Lei Yu
    • , Lori B. Chibnik
    • , Julie A. Schneider
    • , Tracy L. Young-Pearse
    • , David A. Bennett
    •  & Philip L. De Jager
  • Article |

    Chronic morphine use can lead to tolerance and AC superactivation. This paper identifies a molecular mechanism by which V1bR signaling promotes this process, providing a potential approach to enhance morphine analgesia without increasing tolerance.

    • Taka-aki Koshimizu
    • , Kenji Honda
    • , Sachi Nagaoka-Uozumi
    • , Atsuhiko Ichimura
    • , Ikuo Kimura
    • , Michio Nakaya
    • , Nobuya Sakai
    • , Katsushi Shibata
    • , Kentarou Ushijima
    • , Akio Fujimura
    • , Akira Hirasawa
    • , Hitoshi Kurose
    • , Gozoh Tsujimoto
    • , Akito Tanoue
    •  & Yukio Takano
  • Article |

    Social rank determines access to feeding and breeding opportunities. Stagkourakis et al. identify an intrinsically amplifying hypothalamic circuit that can generate intermale attack and aggression reward to influence hierarchical status among males.

    • Stefanos Stagkourakis
    • , Giada Spigolon
    • , Paul Williams
    • , Jil Protzmann
    • , Gilberto Fisone
    •  & Christian Broberger
  • Article |

    The authors revise the classical view that homeostasis of neuronal activity is achieved by negative firing rate feedback: during sensory deprivation, homeostasis occurs via the sliding threshold, which acts via firing patterns rather than rates.

    • Michelle C. D. Bridi
    • , Roberto de Pasquale
    • , Crystal L. Lantz
    • , Yu Gu
    • , Andrew Borrell
    • , Se-Young Choi
    • , Kaiwen He
    • , Trinh Tran
    • , Su Z. Hong
    • , Andrew Dykman
    • , Hey-Kyoung Lee
    • , Elizabeth M. Quinlan
    •  & Alfredo Kirkwood
  • Article |

    Khan et al. simultaneously measured activity from excitatory cells and three classes of inhibitory interneurons in visual cortex and show that learning differentially shapes the stimulus selectivity and interactions of multiple cell classes.

    • Adil G. Khan
    • , Jasper Poort
    • , Angus Chadwick
    • , Antonin Blot
    • , Maneesh Sahani
    • , Thomas D. Mrsic-Flogel
    •  & Sonja B. Hofer
  • Article |

    Humans and other mammals are prodigious learners, partly because they also ‘learn how to learn’. Wang and colleagues present a new theory showing how learning to learn may arise from interactions between prefrontal cortex and the dopamine system.

    • Jane X. Wang
    • , Zeb Kurth-Nelson
    • , Dharshan Kumaran
    • , Dhruva Tirumala
    • , Hubert Soyer
    • , Joel Z. Leibo
    • , Demis Hassabis
    •  & Matthew Botvinick

Resources

  • Resource |

    Using single-cell RNA-seq, the authors produced a comprehensive atlas of the somatosensory spinal cord. They found that neuron types build the dorsal horn by a discrete layering and to be differentially engaged by noxious heat and cold.

    • Martin Häring
    • , Amit Zeisel
    • , Hannah Hochgerner
    • , Puneet Rinwa
    • , Jon E. T. Jakobsson
    • , Peter Lönnerberg
    • , Gioele La Manno
    • , Nilesh Sharma
    • , Lotta Borgius
    • , Ole Kiehn
    • , Malin C. Lagerström
    • , Sten Linnarsson
    •  & Patrik Ernfors

Technical Reports

  • Technical Report |

    The authors present a new approach to create and edit custom spatiotemporal neural activity patterns in awake, behaving animals with extremely high spatial and temporal precision. They present novel opsins optimized for multiphoton optogenetics.

    • Alan R. Mardinly
    • , Ian Antón Oldenburg
    • , Nicolas C. Pégard
    • , Savitha Sridharan
    • , Evan H. Lyall
    • , Kirill Chesnov
    • , Stephen G. Brohawn
    • , Laura Waller
    •  & Hillel Adesnik

Amendments & Corrections