Sizer, S. E. | bioRxiv Science

bioRxiv2025

Glutamate delta-1 receptors regulate a novel 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 ({delta}GluRs, GluD1 and GluD2) are homologs of the AMPARs and NMDARs, 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 they also may supply a tonic excitatory conductance, are sensitive to poly-amine blockade, and regulate synaptic plasticity. Here we use whole-cell patch clamp electrophysiology to functionally characterize these receptors in the dorsolateral bed nucleus of the stria terminalis (dlBNST) and investigate their modulation of both synaptic transmission and cell excitability. Our results suggest that {delta}GluRs, and in particular GluD1, carry a tonic conductance, modulate excitatory synapses, and regulate cell excitability in the dlBNST. These results imply that GluD1 functions to regulate the flow of information through the BNST and may play a role in affect, stress, and substance use disorders.

neuroscience↗

bioRxiv2023

GABA Release From Central Amygdala Neurotensin Neurons Differentially Modulates Reward and Consummatory Behavior in Male and Female Mice

The central nucleus of the amygdala is known to play key roles in alcohol use and affect. Neurotensin neurons in the central nucleus of the amygdala have been shown to regulate alcohol drinking in male mice. However, little is known about which neurotransmitters released by these cells drive alcohol consumption or whether these cells drive alcohol consumption in female mice. Here we show that knockdown of GABA release from central amygdala neurotensin neurons using a Nts-cre-dependent vGAT-shRNA-based AAV strategy reduces alcohol drinking in male, but not female, mice. This manipulation did not impact avoidance behavior, except in a fasted novelty-suppressed feeding test, in which vGAT shRNA mice demonstrated increased latency to feed on a familiar high-value food reward, an effect driven by male mice. In contrast, vGAT shRNA female mice showed heightened sensitivity to thermal stimulation. These data show a role for GABA release from central amygdala neurotensin neurons in modulating consumption of rewarding substances in different motivational states.

neuroscience↗