Distributed circuits underlying anxiety

Abstract

Anxiety is of paramount importance for animals, as it allows assessment of the environment while minimizing exposure to potential threats. Furthermore, anxiety disorders are highly prevalent. Consequently, the neural circuitry underlying anxiety has been a topic of great interest. In this mini review, we will discuss current views on anxiety circuits. We will focus on rodent anxiety paradigms, but we will also consider results from human neuroimaging and clinical studies. We briefly review studies demonstrating the central role that the amygdala and the bed nucleus of the stria terminals (BNST) play in modulating anxiety and present evidence showing how the bed nucleus uses different output pathways to influence specific features of anxiolysis. Lastly, we propose that several brain regions, such as the medial prefrontal cortex (mPFC) and the ventral hippocampus (vHPC), act in a coordinated fashion with the amygdala and BNST, forming a distributed network of interconnected structures that control anxiety both in rodents and humans.

Keywords: BNST; amygdala; anxiety; medial prefrontal cortex; ventral hippocampus.

Figure 1

Simplified scheme of the anxiety network. Highly processed sensory and contextual information from the vHPC and the mPFC is integrated by the BLA, which in turn may activate the CeA and the BNST. The CeA and the BNST project to the hypothalamus and to brain stem nuclei such as the PB, which modulate various features of anxiety, such as avoidance of open spaces and changes in respiration rate. For simplification purposes subregions of the BNST, CeA, Hypothalamus and mPFC are not shown. Abbreviations: BLA: basolateral amygdala, BNST: bed nucleus of the stria terminalis, CeA: central amygdala, Hyp: hypothalamus, mPFC: medial prefrontal cortex, PB: parabrachial nucleus, vHPC: ventral hippocampus.