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

Hans-Christian Pape
Institut für Physiologie I, Westfälische Wilhelms-Universität Münster
The brain circuits underlying behavioral fear have been extensively studied over the last
decades. While the vast majority of experimental studies assess fear as a transient state of
apprehension in response to a discrete threat, such phasic states of fear can shift to a sustained
anxious apprehension, particularly in face of diffuse cues with unpredictable environmental
contingencies. 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.