Abstract
In humans, activation of the ventral striatum, a region associated with reward processing, is associated with the extinction of fear, a goal in the treatment of fear-related disorders. This evidence suggests that extinction of aversive memories engages reward-related circuits, but a causal relationship between activity in a reward circuit and fear extinction has not been demonstrated. Here, we identify a basolateral amygdala (BLA)-ventral striatum (NAc) pathway that is activated by extinction training. Enhanced recruitment of this circuit during extinction learning, either by pairing reward with fear extinction training or by optogenetic stimulation of this circuit during fear extinction, reduces the return of fear that normally follows extinction training. Our findings thus identify a specific BLA-NAc reward circuit that can regulate the persistence of fear extinction and point toward a potential therapeutic target for disorders in which the return of fear following extinction therapy is an obstacle to treatment.
Highlights
Anxiety, trauma, and stress-related disorders have a high lifetime prevalence rate (Kessler et al, 2005) and can be debilitating
To test whether a basolateral amygdala (BLA)-nucleus accumbens (NAc) circuit is engaged by fear extinction, we first used a double-labeling strategy to search for NAc-projecting BLA neurons that could be activated by extinction training after fear conditioning
We labeled BLA neurons projecting to the NAc by infusing a fluorescent retrograde tracer, cholera toxin B (CTB) conjugated to Alexa fluor 488 (Conte et al, 2009), into the NAc to allow subsequent detection of labeled BLA-NAc projecting neurons (Figure 1)
Summary
Trauma, and stress-related disorders have a high lifetime prevalence rate (Kessler et al, 2005) and can be debilitating. The most common treatment for these disorders is exposure therapy, in which trauma-associated or anxiety-provoking cues are presented in a safe environment in order to decrease gradually, or to extinguish, cue-evoked recollection (Rothbaum and Davis, 2003; Felmingham et al, 2013). Traumatic events and exposure therapy are modeled using Pavlovian fear conditioning and extinction training. The CSs are presented in the absence of aversive stimuli in order to decrease CS-elicited fear. Associative fear memories that result from fear conditioning can be extinguished, but they exhibit spontaneous recovery (Quirk, 2002), providing a powerful behavioral model by which to identify and study the neural circuits that support these phenomena
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