Delta glutamate receptor conductance drives excitation of dorsal raphe neurons

The delta glutamate receptors, GluD1R and GluD2R, are mysterious members of the ionotropic glutamate receptor family in that they are not gated by glutamate1,2. One theory is that they are scaffolding proteins or synaptic organizers strictly, rather than ion conducting channels. Although mutant forms and wild type channels have been reported to conduct3,4,5, conduction, gating, and biophysical properties of native GluD1R remain unexplored. Here we show that the inward current induced by activation of 1-adrenergic receptors (1-ARs) in the dorsal raphe nucleus (DR) is mediated by GluD1R. Native GluD1R channels are functional ion channels that are constitutively active under basal conditions and 1-ARs increase the tonic current. This inward current is responsible for the 1-AR-dependent induction of persistent pacemaker-type firing of neurons in the DR. Given the extensive distribution of these receptors, the ionotropic nature of GluDR is proposed to be widespread in the nervous system.