The extended amygdala – what it is and how it regulates responses to predictable and unpredictable threat.

Unpredictability, in turn, is considered an important variable contributing to anxiety disorders. The networks of the so-called extended amygdala, involving the central amygdala and the bed nucleus of the stria terminalis (BNST), have been suggested keys to the control of phasic and sustained components of fear, although the underlying synaptic pathways and mechanisms remain poorly understood. Recent studies using mostly genetic mouse models and optogentic/electrophysiological approaches have revealed dedicated synaptic pathways of the extended amygdala. Within these pathways, transmitters and synaptic proteins involving the endocannabinoiud system have turned out to be causal for regulating the fear response profile during unpredictability of environmental influences. Together, these mechanisms in extended amygdala circuits provide promising entry points to our understanding of anxiety symptoms in humans.