Chemogenetic inhibition of amygdala to ventrolateral prefrontal cortex communication selectively impacts contingent learning

Abstract

Contingent learning, the process by which specific courses of action become associated with subsequent outcomes, is dependent on the amygdala and ventrolateral prefrontal cortex (vlPFC). The amygdala and vlPFC are bidirectionally connected but it is unclear what the contribution of individual feedforward and feedback pathways is to contingent learning. Here we tested the role of amygdala projections to vlPFC in mediating two key components of contingent learning: signaling the outcome (reward/no reward) that follows a choice and maintaining representation of the choice that was made prior to outcome delivery. To test for these two aspects of contingent learning, we trained macaques to perform a probabilistic reward learning task where for separate stimulus pairs reward was either delivered immediately or after a trace interval. Inhibiting vlPFC-projecting amygdala neurons impacted contingent learning irrespective of whether there was a trace interval or not, and this effect was primarily driven by maladaptive learning on unrewarded trials. Notably, deficits in contingent learning caused by manipulating activity in the amygdala-vlPFC pathway were distinct from impairments in motivation and the ability to update the value of specific rewards in a reinforcer devaluation task. Thus, vlPFC-projecting amygdala neurons appear to play a specific role in contingent learning through signaling the outcomes of a choice, but not in maintaining a memory of the prior choice. SIGNIFICANCE STATEMENTImpairments in learning which stimuli or actions are associated with temporally proximate rewards or punishments is characteristic of a host of psychiatric and neurological disorders. Determining the neural circuits that support this type of contingent learning is therefore a key question in neuroscience. Here we show that that during contingent stimulus-reward learning, projections from amygdala to ventrolateral prefrontal cortex (vlPFC) in macaques are essential for signaling reward delivery or omission. These projections appear to be less involved in maintaining a memory of the prior choice that led to the reward or punishment that is subsequently experienced or for updating the value of the received rewards. Thus, amygdala-vlPFC connections make a specific contribution to signaling reward feedback during learning.