Emotional valence interactions in amygdala circuits

Abstract

Survival of organisms crucially depends on their ability to adapt their behavior to changes in environmental circumstances. This adaptation to changes in the emotional significance of environmental cues is acquired through two different types of learning: either through conditioning, when animals learn the predictive relationship between environmental cues and biologically relevant outcomes or, through subsequent extinction learning, when the cue is not predictive anymore of the outcome. The amygdala is crucially involved in the learning processes regarding these changes in valence and contingency between stimuli and biologically relevant outcomes. Here we study at the single neuron level the representation and interaction of conditioning and extinction of opposite valences. We show that the basal nucleus of the amygdala encompasses distinct neuronal subpopulations responsible for learning specific changes in stimulus-outcome contingencies in a valence-dependent manner. We first identify basal amygdala neurons specifically responsive to either aversive conditioned cues, the so-called fear neurons, or exclusively to aversive extinguished cues, the fear extinction neurons. Subsequently, the development of a purely Pavlovian appetitive conditioning allowed us to determine that conditioning and extinction are encoded in a very similar manner in the appetitive and aversive domains. We identify appetitive neurons which are cue-responsive after appetitive conditioning and appetitive extinction neurons only responding to appetitive extinguished cues. The identification of these discrete neuronal populations which activity correlates with high and low emotional states raises the question of how conditioning and extinction of opposite valences are represented relative to each other in basal amygdala circuits. We address this question by combining sequential appetitive and aversive learning with chronic single unit recordings. Conditioning and extinction of opposite valences are mostly encoded in a segregated manner: conditioning neurons of one valence overlap neither with conditioning nor with extinction neurons of the opposite valence. In contrast, extinction neurons of opposite valence partially overlap, suggesting that extinction learning recruits valence-free and valence-independent mechanisms. Although the valence-specific conditioning and extinction neurons appear to be spatially segregated, opposite valences interact with each other in time. We show that prior appetitive experience delays fear extinction learning without affecting fear conditioning. These behavioral findings are corroborated at the neuronal level by the insensitivity of fear neurons to prior appetitive experience whereas the activity of fear extinction neurons is reduced by prior appetitive experience. This demonstrates that prior emotional experience influences subsequent associative learning both at the behavioral and at the neuronal level. Finally, comparison of the basal amygdala responsiveness to aversive and appetitive cues reveals a strong aversive bias of amygdala circuits. Extinction resistant neurons, which post-conditioning cue-responsiveness is maintained after extinction learning, are responsible for this aversive bias. Like the other neuronal populations identified in this study, extinction-resistant neurons of opposite valence are mostly segregated. This suggests that these neurons participate in the maintenance of valence-specific memory traces after extinction learning and thus that aversive memories are more resistant to changes in stimulus-outcome contingency. Supporting this hypothesis, we also find a strong asymmetry of extinction training between aversive and appetitive valence: aversive extinction requiring much longer training than appetitive extinction.