Fear extinction deficits following acute stress associate with increased spine density and dendritic retraction in basolateral amygdala neurons

Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retraction in the medial prefrontal cortex. Here, we examined extinction learning and basolateral amygdala pyramidal neuron morphology in adult male rats following a single elevated platform stress. Acute stress impaired extinction acquisition and memory, and produced dendritic retraction and increased mushroom spine density in basolateral amygdala neurons in the right hemisphere. Unexpectedly, irrespective of stress, rats that underwent fear and extinction testing showed basolateral amygdala dendritic retraction and altered spine density relative to non-conditioned rats, particularly in the left hemisphere. Thus, extinction deficits produced by acute stress are associated with increased spine density and dendritic retraction in basolateral amygdala pyramidal neurons. Furthermore, the finding that conditioning and extinction as such was sufficient to alter basolateral amygdala morphology and spine density illustrates the sensitivity of basolateral amygdala morphology to behavioral manipulation. These findings may have implications for elucidating the role of the amygdala in the pathophysiology of stress-related disorders. Acute stress impaired extinction (A) and produced dendritic retraction in basolateral amygdala (BLA) pyramidal neurons (B). Stress-induced changes in morphology were lateralized to the right hemisphere, whereas behavioral testing produced dendritic retraction in the left hemisphere (C). Right-hemisphere dendritic retraction correlated with extinction deficits (D). Thus, learning and stress produced dissociable changes in BLA morphology. BLA dendritic and synaptic remodeling could contribute to stress-induced impairments in extinction and stress-related disorders. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.