Potentiation of neuronal activity by tonic GluD1 current in brain slices

Ion channel function of native delta glutamate receptors (GluD(R)) is incompletely understood. Previously, we and others have shown that activation of Gαq protein‐coupled receptors (GqPCR) produces a slow inward current carried by GluD1(R). GluD1(R) also carries a tonic cation current of unknown cause. Here, using voltage‐clamp electrophysiological recordings from adult mouse brain slices containing the dorsal raphe nucleus, we find no role of ongoing G‐protein‐coupled receptor activity in generating or sustaining tonic GluD1(R) currents. Neither augmentation nor disruption of G protein activity affects tonic GluD1(R) currents, suggesting that ongoing G‐protein‐coupled receptor activity does not give rise to tonic GluD1(R) currents. Further, the tonic GluD1(R) current is unaffected by the addition of external glycine or D‐serine, which influences GluD2(R) current at millimolar concentrations. Instead, GqPCR‐stimulated and tonic GluD1(R) currents are regulated by physiological levels of external calcium. In current‐clamp recordings, block of GluD1(R) channels hyperpolarizes the membrane by ~7 mV at subthreshold potentials, reducing excitability. Thus, GluD1(R) carries a G‐protein‐independent tonic current that contributes to subthreshold neuronal excitation in the dorsal raphe nucleus.