Abstract

Sensory experience plays an important role in shaping neural circuitry by affecting the synaptic connectivity and intrinsic properties of individual neurons. Identifying the molecular players responsible for converting external stimuli into altered neuronal output remains a crucial step in understanding experience-dependent plasticity and circuit function. Here, we investigate the role of the activity-regulated, non-canonical Ras-like GTPase Rem2 in visual circuit plasticity. We demonstrate that Rem2-/- mice fail to exhibit normal ocular dominance plasticity during the critical period. At the cellular level, our data establish a cell-autonomous role for Rem2 in regulating intrinsic excitability of layer 2/3 pyramidal neurons, prior to changes in synaptic function. Consistent with these findings, both in vitro and in vivo recordings reveal increased spontaneous firing rates in the absence of Rem2. Taken together, our data demonstrate that Rem2 is a key molecule that regulates neuronal excitability and circuit function in the context of changing sensory experience.

Data availability

Imaging data is available at http://www.vhlab.org/data.All other data generated or analyzed during this study is included in the manuscript and supporting files.

Article and author information

Author details

  1. Anna R Moore

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sarah E Richards

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Katelyn Kenny

    National Center for Behavioral Genomics, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Leandro Royer

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Urann Chan

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Kelly Flavahan

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Stephen D Van Hooser

    Department of Biology, Brandeis University, Waltham, United States
    For correspondence
    vanhoosr@brandeis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1112-5832
  8. Suzanne Paradis

    Department of Biology, Brandeis University, Waltham, United States
    For correspondence
    paradis@brandeis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5190-4240

Funding

National Eye Institute (EY022122)

  • Stephen D Van Hooser

National Institute of Mental Health (K01MH101639)

  • Anna R Moore

National Institute of Neurological Disorders and Stroke (R01NS065856)

  • Suzanne Paradis

National Institute of Neurological Disorders and Stroke (Ruth L Kirschstein NIH Training Grant T32NS007292)

  • Anna R Moore

Charles Hood Foundation

  • Stephen D Van Hooser

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental procedures involving animals were performed in strict accordance with the recommendations set forth in the Guide for the Care and Use of Laboratory Animals of the National Institute of Health. All animal handling and experimental procedures were approved by the Institutional Animal Care and Use Committee at Brandeis University (Protocol Numbers: 16002 and 17004). Surgical procedures were performed under sterile conditions and every effort was made to minimize suffering.

Reviewing Editor

  1. Yukiko Goda, RIKEN, Japan

Version history

  1. Received: October 25, 2017
  2. Accepted: May 28, 2018
  3. Accepted Manuscript published: May 29, 2018 (version 1)
  4. Version of Record published: June 20, 2018 (version 2)

Copyright

© 2018, Moore et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,129
    Page views
  • 272
    Downloads
  • 10
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Anna R Moore
  2. Sarah E Richards
  3. Katelyn Kenny
  4. Leandro Royer
  5. Urann Chan
  6. Kelly Flavahan
  7. Stephen D Van Hooser
  8. Suzanne Paradis
(2018)
Rem2 stabilizes intrinsic excitability and spontaneous firing in visual circuits
eLife 7:e33092.
https://doi.org/10.7554/eLife.33092

Further reading

    1. Neuroscience
    Jing Wang, Hamid Azimi ... Gregor Rainer
    Research Article

    The lateral geniculate nucleus (LGN), a retinotopic relay center where visual inputs from the retina are processed and relayed to the visual cortex, has been proposed as a potential target for artificial vision. At present, it is unknown whether optogenetic LGN stimulation is sufficient to elicit behaviorally relevant percepts, and the properties of LGN neural responses relevant for artificial vision have not been thoroughly characterized. Here, we demonstrate that tree shrews pretrained on a visual detection task can detect optogenetic LGN activation using an AAV2-CamKIIα-ChR2 construct and readily generalize from visual to optogenetic detection. Simultaneous recordings of LGN spiking activity and primary visual cortex (V1) local field potentials (LFP) during optogenetic LGN stimulation show that LGN neurons reliably follow optogenetic stimulation at frequencies up to 60 Hz, and uncovered a striking phase locking between the V1 local field potential (LFP) and the evoked spiking activity in LGN. These phase relationships were maintained over a broad range of LGN stimulation frequencies, up to 80 Hz, with spike field coherence values favoring higher frequencies, indicating the ability to relay temporally precise information to V1 using light activation of the LGN. Finally, V1 LFP responses showed sensitivity values to LGN optogenetic activation that were similar to the animal's behavioral performance. Taken together, our findings confirm the LGN as a potential target for visual prosthetics in a highly visual mammal closely related to primates.

    1. Neuroscience
    Yuk-Hoi Yiu, Christian Leibold
    Research Article

    Hippocampal place cell sequences have been hypothesized to serve as diverse purposes as the induction of synaptic plasticity, formation and consolidation of long-term memories, or navigation and planning. During spatial behaviors of rodents, sequential firing of place cells at the theta timescale (known as theta sequences) encodes running trajectories, which can be considered as one-dimensional behavioral sequences of traversed locations. In a two-dimensional space, however, each single location can be visited along arbitrary one-dimensional running trajectories. Thus, a place cell will generally take part in multiple different theta sequences, raising questions about how this two-dimensional topology can be reconciled with the idea of hippocampal sequences underlying memory of (one-dimensional) episodes. Here, we propose a computational model of cornu ammonis 3 (CA3) and dentate gyrus (DG), where sensorimotor input drives the direction-dependent (extrinsic) theta sequences within CA3 reflecting the two-dimensional spatial topology, whereas the intrahippocampal CA3-DG projections concurrently produce intrinsic sequences that are independent of the specific running trajectory. Consistent with experimental data, intrinsic theta sequences are less prominent, but can nevertheless be detected during theta activity, thereby serving as running-direction independent landmark cues. We hypothesize that the intrinsic sequences largely reflect replay and preplay activity during non-theta states.