Abstract
Stress exposure, depending on its intensity and duration, affects cognition and learning in an adaptive or maladaptive manner. Studies addressing the effects of stress on cognitive processes have mainly focused on conditioned fear, since it is suggested that fear-motivated learning lies at the root of affective and anxiety disorders. Inhibition of fear-motivated response can be accomplished by experimental extinction of the fearful response to the fear-inducing stimulus. Converging evidence indicates that extinction of fear memory requires plasticity in both the medial prefrontal cortex and the amygdala. These brain areas are also deeply involved in mediating the effects of exposure to stress on memory. Moreover, extensive evidence indicates that gamma-aminobutyric acid (GABA) transmission plays a primary role in the modulation of behavioral sequelae resulting from a stressful experience, and may also partially mediate inhibitory learning during extinction. In this review, we present evidence that exposure to a stressful experience may impair fear extinction and the possible involvement of the GABA system. Impairment of fear extinction learning is particularly important as it may predispose some individuals to the development of posttraumatic stress disorder. We further discuss a possible dysfunction in the medial prefrontal cortex-amygdala circuit following a stressful experience that may explain the impaired extinction caused by exposure to a stressor.
Highlights
Pavlovian fear conditioning is an extensively studied model for stress and anxiety-like disorders [1]
In addition to evidence indicating that extinction of fear memory requires plasticity in both the medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) [17,18,19], recent studies further point to a dysfunctional interaction between the prefrontal cortex and the amygdala in the failure to extinguish conditioned fear
We propose that GABAA neurotransmission in the infralimbic cortex plays a facilitatory role in triggering the onset of fear extinction and its maintenance, whereas in the BLA, GABAA neurotransmission facilitates extinction consolidation
Summary
Pavlovian fear conditioning is an extensively studied model for stress and anxiety-like disorders [1]. Even the completely extinguished fear can be recovered spontaneously after the passage of time [9, 10], or be “reinstated” by presentations of the US alone [11, 12], or be renewed by placing the animal in a context different from the one in which it was extinguished [13] This is congruent with the notion that extinction is a form of relearning (of a CS-no US or “inhibitory” association) rather than unlearning (of the CS-US association) [14]. Despite the efficacy of behavior therapy for human anxiety disorders, extinction-like treatments require repeated cue exposures and are vulnerable to reversal by a number of environmental factors, stress. We will discuss the relevance of the prefrontal cortex-amygdala circuit as a key mechanism for understanding stress-induced alterations occurring during the extinction of fear
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