Glutamate delta-1 receptors regulate a tonic excitatory conductance in the mouse bed nucleus of the stria terminalis and influence neuronal function

The plasticity of ionotropic receptors (mainly AMPARs and NMDARs) within the glutamatergic system has long been investigated as a mechanism for physiological and pathological adaptive learning. The tetrameric delta glutamate receptors (δGluRs, GluD1 and GluD2) are also classified as ionotropic glutamate receptors, however they are insensitive to glutamate. These proteins, especially GluD1, have been implicated in multiple psychiatric conditions and play a functional role in synapses assembly and stability, but recent evidence suggests that they also may supply a tonic excitatory conductance, are sensitive to poly-amine blockade, and regulate synaptic plasticity. GluD1 expression has been noted in the dorsolateral bed nucleus of the stria terminalis (dlBNST), but its function in this region remains unknown. We aimed to functionally characterize δGluRs in the dlBNST and investigate their modulation of both synaptic transmission and cell excitability. We used whole-cell patch clamp electrophysiology in male C57BL/6J, GluD1 knockout, and wildtype littermate mice to investigate GluD1 function in the BNST. Our results suggest that GluD1 carries a tonic conductance, modulates excitatory synapses, and regulates cell excitability in the dlBNST. These results imply that GluD1 functions to regulate the flow of information through the BNST and modulation of GluD1 funciton could likely contribute to affective behavior governed by the BNST.