Prefrontal cortical regulation of fear learning

•Prefrontal cortex is necessary for the initial learning of complex fear associations.•Trace and contextual fear paradigms offer insight into cortical control of fear learning.•Emerging evidence suggests prefrontal cortex may modulate standard fear conditioning.•We review recent findings of an expanded role for prefrontal cortex in fear regulation.

The prefrontal cortex regulates the expression of fear based on previously learned information. Recently, this brain area has emerged as being crucial in the initial formation of fear memories, providing new avenues to study the neurobiology underlying aberrant learning in anxiety disorders. Here we review the circumstances under which the prefrontal cortex is recruited in the formation of memory, highlighting relevant work in laboratory animals and human subjects. We propose that the prefrontal cortex facilitates fear memory through the integration of sensory and emotional signals and through the coordination of memory storage in an amygdala-based network.