The ability to appropriately integrate and respond to rewarding and aversive stimuli is essential for survival. The ventral pallidum (VP) plays a critical role in processing both rewarding and aversive stimuli. However, the VP is a heterogeneous structure, and how VP subpopulations integrate into larger reward networks to ultimately modulate these behaviors is not known. Using neurochemical, genetic, and electrophysiology approaches, we characterized glutamatergic VP neurons. Glutamatergic VP neurons exhibit little overlap with cholinergic or gamma-aminobutyric acidergic markers, the canonical VP subtypes, and exhibit distinct membrane properties. Glutamatergic VP neurons innervate and increase firing activity of the lateral habenula, rostromedial tegmental nucleus, and gamma-aminobutyric acidergic ventral tegmental area neurons. While nonselective optogenetic stimulation of the VP induced a robust place preference, selective activation of glutamatergic VP neurons induced a place avoidance. Viral ablation of glutamatergic VP neurons increased reward responding and abolished taste aversion to sucrose. These data support a model in which a glutamatergic VP neurons adaptively constrain reward seeking in the face of aversive stimuli, by modulating habenula and tegmental circuitry.
In the April, 2019 issue of Current Opinion in Neurobiology, read about neuromodulation interventions being applied for substance use disorders, and how pre-clinical studies of circuit function can inform novel therapies. The highlights:
• Clinical studies support the use of STN-DBS and NAc-DBS for treating addiction.
• Pre-clinical studies can inform DBS parameters by elucidating underlying mechanisms.
• Novel paradigms normalize circuit function to reduce behavioral symptoms of addiction.
• New targets, frequencies and technologies are promising avenues for optimizing stimulation.