From safety to frustration: The neural substrates of inhibitory learning in aversive and appetitive conditioning procedures

Abstract

Inhibitory associative learning counters the effects of excitatory learning, whether appetitively or aversively motivated. Moreover, the affective responses accompanying the inhibitory associations are of opponent valence to the excitatory conditioned responses. Inhibitors for negative aversive outcomes (e.g. shock) signal safety, while inhibitors for appetitive outcomes (e.g. food reward) elicit frustration and/or disappointment. This raises the question as to whether studies using appetitive and aversive conditioning procedures should demonstrate the same neural substrates for inhibitory learning. We review the neural substrates of appetitive and aversive inhibitory learning as measured in different procedural variants and in the context of the underpinning excitatory conditioning on which it depends. The mesocorticolimbic dopamine pathways, retrosplenial cortex and hippocampus are consistently implicated in inhibitory learning. Further neural substrates identified in some procedural variants may be related to the specific motivation of the learning task and modalities of the learning cues. Finally, we consider the translational implications of our understanding of the neural substrates of inhibitory learning, for obesity and addictions as well as for anxiety disorders.

Keywords: Amygdala; Appetitively motivated; Aversively motivated; Conditioned inhibition; Differential inhibition; Dopamine; Feature negative discrimination; Prefrontal cortex; Retrosplenial cortex; Ventral tegmental area.