Delta glutamate receptor conductance drives excitation of dorsal raphe neurons

The delta glutamate receptors, GluD1 R and GluD2 R , are mysterious members of the ionotropic glutamate receptor family in that they are not gated by glutamate 1,2 . 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 conduct 3,4,5 , conduction, gating, and biophysical properties of native GluD1 R remain unexplored. Here we show that the inward current induced by activation of α1-adrenergic receptors (α1-A R s) in the dorsal raphe nucleus (DR) is mediated by GluD1 R . Native GluD1 R channels are functional ion channels that are constitutively active under basal conditions and α1-A R s increase the tonic current. This inward current is responsible for the α1-A R -dependent induction of persistent pacemaker-type firing of neurons in the DR. Given the extensive distribution of these receptors, the ionotropic nature of GluD R is proposed to be widespread in the nervous system.