Rem2 stabilizes intrinsic excitability and spontaneous firing in visual circuits
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.
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
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.
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.
- Yukiko Goda, RIKEN, Japan
- Received: October 25, 2017
- Accepted: May 28, 2018
- Accepted Manuscript published: May 29, 2018 (version 1)
- Version of Record published: June 20, 2018 (version 2)
© 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.
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