Chapter 21 - Maladaptive learning and the amygdala—prefrontal circuit

Abstract

The study of anxiety disorders in neuroscience is framed as maladaptive learning and poor emotion regulation. The neural mechanisms underlying adaptive learning intertwine with emotion regulation in tasks that probe learning and memory of threat and reward. Task-related communication between the basolateral complex of the amygdala (BLA) and the medial prefrontal cortex (mPFC) has emerged as a cornerstone of successful evaluation and memory for whether a cue poses a threat. The importance of a functional mPFC–BLA circuit is evident in all aspects of adaptive learning, from initial stimulus encoding and response modulation to recall and extinction of learned associations. First, we outline BLA function as an early detector and encoder of stimuli with different valences. Then, we describe a mixed selectivity stimulus encoding strategy in the mPFC. Next, we show how across species the mPFC–BLA circuit is engaged in discriminative learning from the beginning, when BLA-to-mPFC directionality predominates, to later in training, when mPFC-to-BLA directionality is more prominent. Here, we focus on theta and gamma oscillation changes in the mPFC–BLA circuit and what they may mean for encoding and recall of safety and danger. Throughout, our discussion is mindful of how deficient mPFC–BLA interactions are manifest in disorders of anxiety and are a biological marker of generalized fear. Targeted clinical applications for the mPFC–BLA circuit will emerge from experiments that combine behavioral tasks with techniques that allow us to record, visualize, and manipulate specific circuits in vivo.