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

Christian Bravo-Rivera,Ciorana Roman-Ortiz,Marlian Montesinos-Cartagena,Gregory J Quirk

doi:10.3389/fnbeh.2015.00184

Christian Bravo-Rivera, Ciorana Roman-Ortiz + Show 2 more

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https://doi.org/10.3389/fnbeh.2015.00184

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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.

Highlights

To ensure survival, individuals must learn to actively avoid cues predictive of danger
In order to distinguish between these two possibilities, we modified the task by removing the platform during extinction training, and fully extinguishing the toneshock association to criterion (Figure 2A)
When extinction tones were delivered in the presence of the platform (Task 1), persistent avoidance resembled deficient extinction of toneshock associations, as evidenced by high freezing and c-Fos expression patterns

Summary

Introduction

Individuals must learn to actively avoid cues predictive of danger. Active avoidance can be extinguished when the cues no longer predict danger. The majority of studies focus on neural mechanisms of avoidance acquisition (Gabriel et al, 1983; Orona and Gabriel, 1983; Gabriel, 1990; Maren et al, 1991; Savonenko et al, 1999; Holahan and White, 2002; Lázaro-Muñoz et al, 2010; Shumake et al, 2010; Darvas et al, 2011; Moscarello and LeDoux, 2013; Beck et al, 2014; Lichtenberg et al, 2014; Ramirez et al, 2015), but few focus on its extinction (Gabriel et al, 1983; Pang et al, 2010; Jiao et al, 2011; Bravo-Rivera et al, 2014b; Wendler et al, 2014). Pharmacological inactivation of prelimbic prefrontal cortex (PL) or ventral striatum (VS), but not infralimbic cortex (IL), impaired avoidance expression, whereas inactivation of the IL prior to avoidance extinction impaired retrieval of extinction the following day

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