Persistent active avoidance correlates with activity in prelimbic cortex and ventral striatum

Abstract

Persistent avoidance is a prominent symptom of anxiety disorders and is often resistant to extinction-based therapies. Little is known about the circuitry mediating persistent avoidance. Using a recently described platform-mediated active avoidance task, we assessed activity in several structures with c-Fos immuno-labeling. In Task 1, rats were conditioned to avoid a tone-signaled shock by moving to a safe platform, and then were extinguished over two days. One day later, failure to retrieve extinction correlated with increased activity in the prelimbic prefrontal cortex (PL), ventral striatum (VS), and basal amygdala (BA), and decreased activity in infralimbic prefrontal cortex (IL), consistent with pharmacological inactivation studies. In Task 2, the platform was removed during extinction training and fear (suppression of bar pressing) was extinguished to criterion over 3–5 days. The platform was then returned in a post-extinction test. Under these conditions, avoidance levels were equivalent to Experiment 1 and correlated with increased activity in PL and VS, but there was no correlation with activity in IL or BA. Thus, persistent avoidance can occur independently of deficits in fear extinction and its associated structures.

An Avoidance-Based Rodent Model of Exposure With Response Prevention Therapy for Obsessive-Compulsive Disorder

“…If so, reducing fear with pharmacological adjuncts such as the beta-blocker propranolol (28, 29) might reduce ERP failure. However, it is possible to observe persistent avoidance in the absence of elevated fear in animals (30), healthy humans (31), and OCD patients (32), suggesting that factors other than elevated fear can elicit persistent avoidance.…”

The birth, death and resurrection of avoidance: a reconceptualization of a troubled paradigm

“…Much of the historical work on avoidance has used this approach, and the underlying circuits that have been discovered in recent work are illustrated in Figure 3. Where appropriate, we also describe studies that have used avoidance responses such as lever-pressing 27, 32 or stepping onto a platform 29, 35 to avoid shock in the presence of a CS.…”

“…NAcc has been implicated in appetitive instrumental behavior 136, 202–207 , as have BA neurons that project to NAcc 205, 208–210 . Recent findings demonstrate that active avoidance requires NAcc 29, 33, 35, 211–215 , as well as the flow of information from BA to NAcc 211 . Thus, while LA is common to the circuits of reaction and action, distinct outputs of LA give rise to different amygdala output pathways underlying freezing reactions (CeA-PAG) and avoidance actions (BA-NAcc).…”

“…Future work should explore the role of the striatal habit circuit in well-trained avoidance behaviors. Additionally, activity in the prelimbic region of the prefrontal cortex correlates with avoidance behavior that persists under extinction conditions 29 . We interpret these data to suggest a role for prelimbic prefrontal cortex in defensive habits that continue despite a reduced connection with reinforcing stimuli.…”

Prefrontal circuits signaling active avoidance retrieval and extinction

“…In addition to BLA and VS, we observed that the prelimbic prefrontal cortex (PL-PFC) is necessary for retrieval of previously learned platform-mediated avoidance (Bravo-Rivera et al 2014), where rats pressing a bar for sucrose pellets can step onto a nearby platform to avoid a tone-signaled footshock. Furthermore, rats with excessive avoidance (following deficient extinction learning) show elevated activity in PL, BLA, and VS as indicated by c-Fos expression (Bravo-Rivera et al 2015b). Thus, cortical regulation of avoidance retrieval by PL neurons could occur via direct projections to either BLA or VS (Vertes 2004).…”