Available online 6 March 2026, 102607

Appropriate valence processing, a mechanism believed to assign emotional value to salient stimuli, is a pivotal element of responsive behavior. Malfunctioning of valence processing may compromise behavioral adaptation and facilitate the formation of disordered mental states. The bed nucleus of the stria terminalis (BNST), an essential part of the extended amygdala, has emerged as a sexually dimorphic forebrain area regulating positive and negative emotions. However, due to its structural and functional complexity, the contribution of individual BNST subpopulations remains elusive. Here, we investigated the role of somatostatin (SST)-expressing BNST neurons in valence processing and salience detection. We found that aversive challenges activate GABAergic BNST neurons, particularly those in the oval BNST co-expressing SST, but not coexisting glutamatergic BNST neurons. Interestingly, only the exogenous activation of SST GABA neurons resulted in conditioned place aversion both in male and female mice, while overall activation of BNST-GABA neurons did not promote aversive behavior. This indicates that especially BNST SST neurons serve as essential detectors of salient stimuli initiating the generation of adaptive behavioral responses and significantly contribute to negative valence processing. Neuropeptide-expressing forebrain circuities may thus crystalize as essential substrate for the maintenance of emotional-affective homeostasis.

Amygdala

Bed nucleus of the stria terminalis

BNST

Somatostatin

Valence

Aversion

© 2026 The Authors. Published by Elsevier Ltd.