Motivation under aversive conditions is regulated by a striatopallidal pathway in primates

Motivation often diminishes under aversive conditions. Clinically, motivational deficits are linked to psychiatric disorders such as depression and schizophrenia, yet the neural mechanisms by which aversive contexts suppress motivation remain unclear. Although classical theories associate motivation with the expected value of outcomes, less is known about the neural circuits that govern effort-based behavioral initiation. To address this, we dissociated motivational drive from goal valuation using an approach-avoidance (Ap-Av) task, in which macaques evaluated outcomes combining reward and punishment (air puffs to the face). As a control, we employed an approach-approach (Ap-Ap) task based solely on reward. Using chemogenetic manipulation, we found that selective inhibition of the ventral striatum to ventral pallidum (VS-VP) pathway restored the motivation to initiate trials in the Ap-Av task without affecting goal valuation. No effects were observed in the Ap-Ap task. These findings provide causal evidence that the VS-VP pathway mediates motivational suppression in aversive contexts. Electrophysiological recordings revealed rapid VS responses to aversive cues and a gradual decrease in VP activity, suggesting an inhibitory interaction in which elevated VS activity dampens VP output to limit initiation. The slower VP dynamics may reflect a process by which aversive signals are gradually integrated to influence the motivational state. Together, these results identify the VS-VP pathway as a key circuit by which aversive contexts suppress effort-based behavioral initiation, highlighting it as a potential target for treating motivational deficits in depression and schizophrenia.

DREADDs; approach-avoidance conflict; aversion; avolition; major depressive disorder; motivation; neuromodulation; nonhuman primates; ventral pallidum; ventral striatum.