Delta glutamate receptor conductance drives excitation of mouse dorsal raphe neurons

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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-A_R) activation. Despite this crucial role, the ion channels responsible for a1-A_R-mediated depolarization are unknown. Here, we show in mouse brain slices that a1-A_R-mediated excitatory synaptic transmission is mediated by the ionotropic glutamate receptor homolog cation channel, delta glutamate receptor 1 (GluD1). GluD1_R-channels are constitutively active under basal conditions carrying tonic inward current and synaptic activation of a1-A_Rs augments tonic GluD1_R-channel current. Further, loss of dorsal raphe GluD1_R-channels produces an anxiogenic phenotype. Thus, GluD1_R-channels are responsible for a1-A_R-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 GluD1_R as a regulator of neuronal excitability is proposed to be widespread in the nervous system.

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All data analysed for this study are included in the manuscript.

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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.

"This ORCID iD identifies the author of this article:" 0000-0002-1800-4400
Khaled Moussawi

National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
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.

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.