Emerging themes in fear extinction neurocircuitry, including dopaminergic prediction error, excitatory/inhibitory balance and novel therapeutic strategies

The balance between the learning of fearful events against safety is critically important for adaptive behavioural responses in human and non-human animals. Safety learning can occur through the extinction of fear memory; a new, inhibitory memory that competes with the original fear memory. In this brief review, we provide an update on rodent-based mechanistic insights into the canonical fear extinction neurocircuitry (basolateral amygdala, medial prefrontal cortex and hippocampus), before considering the role of distributed extinction circuits. Next, we focus on emerging themes in specific circuitry and neural substrates including i) dopaminergic-dependent prediction error coding, ii) glutamatergic signalling through NMDA receptors and iii) excitatory and inhibitory (E/I) balance at local synaptic, inhibitory gating and engram levels. Last, we consider whether our increased understanding of fear extinction neurocircuitry has led to development of novel therapeutic strategies, including L-DOPA and D-cycloserine compounds, aimed at augmenting impaired fear extinction in psychopathology.