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.
All data analysed for this study are included in the manuscript.
- Stephanie C Gantz
- 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.
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.
- Olivier J Manzoni, Aix-Marseille University, INSERM, INMED, France
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