Delta glutamate receptor conductance drives excitation of mouse dorsal raphe neurons

• Published in: eLife Vol. 9
• Main Authors: Gantz, Stephanie C, Moussawi, Khaled, Hake, Holly S
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 01-04-2020; eLife Sciences Publications, Ltd
• Subjects: Action potential; Action Potentials - physiology; Adrenergic receptors; alpha1-adrenergic receptor; Animals; Brain slice preparation; delta glutamate receptor; Depolarization; Dorsal raphe nucleus; Dorsal Raphe Nucleus - physiology; Emotional behavior; Excitability; G protein-coupled receptor; Glutamic acid receptors; Hemodialysis; Ion channels; leak current; Mice; Nervous system; Neurons; Neurons - physiology; Neuroscience; noradrenaline; Phenotypes; Potassium; Proteins; Raphe nuclei; Receptors, Adrenergic, alpha-1 - metabolism; Receptors, Glutamate - metabolism; Serotonin; Serotonin - metabolism; Structural Biology and Molecular Biophysics; Synaptic transmission; G protein-coupled receptor; delta glutamate receptor; mouse; serotonin; neuroscience; leak current; noradrenaline; structural biology; molecular biophysics; alpha1-adrenergic receptor
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.56054

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 α1-adrenergic receptors (α1-A
) activation. Despite this crucial role, the ion channels responsible for α1-A
-mediated depolarization are unknown. Here, we show in mouse brain slices that α1-A
-mediated excitatory synaptic transmission is mediated by the ionotropic glutamate receptor homolog cation channel, delta glutamate receptor 1 (GluD1). GluD1
-channels are constitutively active under basal conditions carrying tonic inward current and synaptic activation of α1-A
s augments tonic GluD1
-channel current. Further, loss of dorsal raphe GluD1
-channels produces an anxiogenic phenotype. Thus, GluD1
-channels are responsible for α1-A
-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
as a regulator of neuronal excitability is proposed to be widespread in the nervous system.