Altered activity of the medial prefrontal cortex and amygdala during acquisition and extinction of an active avoidance task.

Xilu Jiao,Catherine E Myers,Kevin D Beck,Kevin C H Pang,Richard J Servatius

doi:10.3389/fnbeh.2015.00249

Abstract

Altered medial prefrontal cortex (mPFC) and amygdala function is associated with anxiety-related disorders. While the mPFC-amygdala pathway has a clear role in fear conditioning, these structures are also involved in active avoidance. Given that avoidance perseveration represents a core symptom of anxiety disorders, the neural substrate of avoidance, especially its extinction, requires better understanding. The present study was designed to investigate the activity, particularly, inhibitory neuronal activity in mPFC and amygdala during acquisition and extinction of lever-press avoidance in rats. Neural activity was examined in the mPFC, intercalated cell clusters (ITCs) lateral (LA), basal (BA) and central (CeA) amygdala, at various time points during acquisition and extinction, using induction of the immediate early gene product, c-Fos. Neural activity was greater in the mPFC, LA, BA, and ITC during the extinction phase as compared to the acquisition phase. In contrast, the CeA was the only region that was more activated during acquisition than during extinction. Our results indicate inhibitory neurons are more activated during late phase of acquisition and extinction in the mPFC and LA, suggesting the dynamic involvement of inhibitory circuits in the development and extinction of avoidance response. Together, these data start to identify the key brain regions important in active avoidance behavior, areas that could be associated with avoidance perseveration in anxiety disorders.

Highlights

Avoidance is a common feature of anxiety disorders (American Psychiatric Association, 2000)
These data suggest that rats in each of the groups acquired and extinguished avoidance responses and that observed difference in immediate early gene product is likely resulting from training phases and training stages
In the medial prefrontal cortex (mPFC) and most amygdalar sub-regions, activity increased in late acquisition sessions (A08–A10) when avoidance response was acquired and peaked in extinction phase when shock was no longer present

Summary

Introduction

Avoidance is a common feature of anxiety disorders (American Psychiatric Association, 2000). Malfunctions in medial prefrontal cortex (mPFC)—amygdala circuit have been identified in patients suffering PTSD, social anxiety disorder (SAD) and general anxiety disorder (GAD; Schwartz and Rauch, 2004; Cottraux, 2005; Guyer et al, 2008). Imaging studies indicate that one of the most consistent findings in PTSD patients is hypoactive ventral mPFC combined with hyperactive amygdala following provocation (Milad et al, 2006; Phan et al, 2006; Rauch et al, 2006). Avoidance develops slowly over time in anxiety disorders, so avoidance learning in animals may provide an opportunity to study the dynamic and progressive neurobiological changes associated with the development of anxiety disorders

Methods

Results

Conclusion