Rem2 stabilizes intrinsic excitability and spontaneous firing in visual circuits
- Brandeis University, United States
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
Stephen D Van Hooser
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
- Yukiko Goda, RIKEN, Japan
Publication history
- 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)
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
-
- 2,068
- Page views
-
- 262
- 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)
Rem2 stabilizes intrinsic excitability and spontaneous firing in visual circuits
eLife 7:e33092.
https://doi.org/10.7554/eLife.33092
Further reading
-
- Developmental Biology
- Neuroscience
How does wiring specificity of neural maps emerge during development? Formation of the adult Drosophila olfactory glomerular map begins with patterning of projection neuron (PN) dendrites at the early pupal stage. To better understand the origin of wiring specificity of this map, we created genetic tools to systematically characterize dendrite patterning across development at PN type-specific resolution. We find that PNs use lineage and birth order combinatorially to build the initial dendritic map. Specifically, birth order directs dendrite targeting in rotating and binary manners for PNs of the anterodorsal and lateral lineages, respectively. Two-photon- and adaptive optical lattice light-sheet microscope-based time-lapse imaging reveals that PN dendrites initiate active targeting with direction-dependent branch stabilization on the timescale of seconds. Moreover, PNs that are used in both the larval and adult olfactory circuits prune their larval-specific dendrites and re-extend new dendrites simultaneously to facilitate timely olfactory map organization. Our work highlights the power and necessity of type-specific neuronal access and time-lapse imaging in identifying wiring mechanisms that underlie complex patterns of functional neural maps.
-
- Neuroscience
Comparing connectomes can help explain how neural connectivity is related to genetics, disease, development, learning, and behavior. However, making statistical inferences about the significance and nature of differences between two networks is an open problem, and such analysis has not been extensively applied to nanoscale connectomes. Here, we investigate this problem via a case study on the bilateral symmetry of a larval Drosophila brain connectome. We translate notions of'bilateral symmetry' to generative models of the network structure of the left and right hemispheres, allowing us to test and refine our understanding of symmetry. We find significant differences in connection probabilities both across the entire left and right networks and between specific cell types. By rescaling connection probabilities or removing certain edges based on weight, we also present adjusted definitions of bilateral symmetry exhibited by this connectome. This work shows how statistical inferences from networks can inform the study of connectomes, facilitating future comparisons of neural structures.
