Aversive stimuli can impact motivation and support associative learning as reinforcers. However, the neural circuitry underlying the processing of aversive reinforcers has not been elucidated. Here, we report that a subpopulation of central amygdala (CeA) GABAergic neurons expressing protein kinase C-delta (PKC-δ+) displays robust responses to aversive stimuli during negative reinforcement learning. Importantly, projections from PKC-δ+ neurons of the CeA to the substantia innominata (SI) could bi-directionally modulate negative reinforcement learning. Moreover, consistent with the idea that SI-projecting PKC-δ+ neurons of the CeA encode aversive information, optogenetic activation of this pathway produces conditioned place aversion, a behavior prevented by simultaneous ablating of SI glutamatergic neurons. Taken together, our data define a cell-type-specific neural circuitry modulating associative learning by encoding aversive reinforcement signals.

Figure 1. CeL_PKC-d+ Neurons Project to the SI.

This study is aimed to explore the neural circuitry underlying the processing of aversive reinforcers. The authors investigated the role of CeL_PKC-d+ and CeL_SOM+ neurons in a go/no-go associative learning task. The data uncovered a previously unknown function of the CeL_PKC-d+-SIV_gluT2+ neural circuitry to modulate negative reinforcement learning by encoding aversive signals.