Delta glutamate receptor conductance drives excitation of mouse dorsal raphe neurons.

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 ?1-adrenergic receptors (?1-A_R) activation. Despite this crucial role, the ion channels responsible for ?1-A_R-mediated depolarization are unknown. Here, we show in mouse brain slices that ?1-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 ?1-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 ?1-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.

SUBMITTER: Gantz SC 

PROVIDER: S-EPMC7180053 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature