Salience processing by glutamatergic neurons in the ventral pallidum

Organisms must make sense of a constant stream of sensory inputs from both internal and external sources which compete for attention by determining which ones are salient. The ability to detect and respond appropriately to potentially salient stimuli in the environment is critical to all organisms. However, the neural circuits that process salience are not fully understood. Here, we identify a population of glutamatergic neurons in the ventral pallidum (VP) that play a unique role in salience processing. Using cell-type-specific fiber photometry, we find that VP glutamatergic neurons are robustly activated by a variety of aversion- and reward-related stimuli, as well as novel social and non-social stimuli. Inhibition of the VP glutamatergic neurons reduces the ability to detect salient stimuli in the environment, such as aversive cue, novel conspecific and novel object. Besides, VP glutamatergic neurons project to both the lateral habenula (LHb) and the ventral tegmental area (VTA). Together, our findings demonstrate that the VP glutamatergic neurons participate in salience processing and therefore provide a new perspective on treating several neuropsychiatric disorders, including dementia and psychosis.