1. Neuroscience
  2. Structural Biology and Molecular Biophysics
Download icon

Delta glutamate receptor conductance drives excitation of mouse dorsal raphe neurons

  1. Stephanie C Gantz  Is a corresponding author
  2. Khaled Moussawi
  3. Holly S Hake
  1. National Institutes of Health, United States
Research Article
  • Cited 6
  • Views 1,254
  • Annotations
Cite this article as: eLife 2020;9:e56054 doi: 10.7554/eLife.56054

Abstract

The dorsal raphe nucleus is the predominant source of central serotonin, where neuronal activity regulates complex emotional behaviors. Action potential firing of serotonin dorsal raphe neurons is driven via a1-adrenergic receptors (a1-AR) activation. Despite this crucial role, the ion channels responsible for a1-AR-mediated depolarization are unknown. Here, we show in mouse brain slices that a1-AR-mediated excitatory synaptic transmission is mediated by the ionotropic glutamate receptor homolog cation channel, delta glutamate receptor 1 (GluD1). GluD1R-channels are constitutively active under basal conditions carrying tonic inward current and synaptic activation of a1-ARs augments tonic GluD1R-channel current. Further, loss of dorsal raphe GluD1R-channels produces an anxiogenic phenotype. Thus, GluD1R-channels are responsible for a1-AR-dependent induction of persistent pacemaker-type firing of dorsal raphe neurons and regulate dorsal raphe-related behavior. Given the widespread distribution of these channels, ion channel function of GluD1R as a regulator of neuronal excitability is proposed to be widespread in the nervous system.

Article and author information

Author details

  1. Stephanie C Gantz

    National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    For correspondence
    stephanie.gantz@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1800-4400
  2. Khaled Moussawi

    National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Holly S Hake

    National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

NIH Center on Compulsive Behaviors (Center on Compulsive Behaviors Fellowship)

  • Stephanie C Gantz

National Institute on Drug Abuse

  • Stephanie C Gantz
  • Khaled Moussawi
  • Holly S Hake

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

Ethics

Animal experimentation: This study was conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory animals. The protocol was approved by the National Institute on Drug Abuse Animal Care and Use Committee.

Reviewing Editor

  1. Olivier J Manzoni, Aix-Marseille University, INSERM, INMED, France

Publication history

  1. Received: February 14, 2020
  2. Accepted: April 1, 2020
  3. Accepted Manuscript published: April 1, 2020 (version 1)
  4. Version of Record published: April 23, 2020 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 1,254
    Page views
  • 204
    Downloads
  • 6
    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)

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

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

Further reading

    1. Neuroscience
    María Fernanda López-Gutiérrez et al.
    Research Article

    Previous studies have related pair bonding in Microtus ochrogaster, the prairie vole, with plastic changes in several brain regions. However, the interactions between these socially-relevant regions have yet to be described. In this study, we used resting state magnetic resonance imaging to explore bonding behaviors and functional connectivity of brain regions previously associated with pair bonding. Thirty-two male and female prairie voles were scanned at baseline, 24h and 2 weeks after the onset of cohabitation By using network based statistics, we identified that the functional connectivity of a cortico-striatal network predicted the onset of affiliative behavior, while another predicted the amount of social interaction during a partner preference test. Furthermore, a network with significant changes in time was revealed, also showing associations with the level of partner preference. Overall, our findings revealed the association between network-level functional connectivity changes and social bonding.

    1. Developmental Biology
    2. Neuroscience
    Alessia Caramello et al.
    Research Article Updated

    During embryonic development, radial glial cells give rise to neurons, then to astrocytes following the gliogenic switch. Timely regulation of the switch, operated by several transcription factors, is fundamental for allowing coordinated interactions between neurons and glia. We deleted the gene for one such factor, SOX9, early during mouse brain development and observed a significantly compromised dentate gyrus (DG). We dissected the origin of the defect, targeting embryonic Sox9 deletion to either the DG neuronal progenitor domain or the adjacent cortical hem (CH). We identified in the latter previously uncharacterized ALDH1L1+ astrocytic progenitors, which form a fimbrial-specific glial scaffold necessary for neuronal progenitor migration toward the developing DG. Our results highlight an early crucial role of SOX9 for DG development through regulation of astroglial potential acquisition in the CH. Moreover, we illustrate how formation of a local network, amidst astrocytic and neuronal progenitors originating from adjacent domains, underlays brain morphogenesis.