Figure 3. Pavlovian fear conditioning circuitry.

In cue fear conditioning, animals learn to fear an innocuous stimulus, such as a tone. By pairing tone (conditioned stimulus: CS) and shock (unconditioned stimulus: US), the tone acquires the capacity to elicit defensive reactions, such as freezing (arrow pointing up). Tone and shock stimuli converge in the lateral amygdala (LA), resulting in associative plasticity in the tone→LA pathway. Subsequent presentations of the tone can now activate LA neurons. The LA then communicates with the central nucleus (CE), which controls the expression of fear by way of connections to specific circuits that mediate fear reactions (e.g. freezing, potentiated startle, autonomic responses and hormonal responses). The LA connects with CE directly and by way of connections to other amygdala areas, including the intercalated cell masses (ICM), which gate the output, and the basal nucleus (B), which processes contextual information from the hippocampus. As with discrete CSs, more complex configural cues can also enter into associations with the US via hippocampal connections to the basolateral amygdala. CRF and CRF₁ receptors are present throughout fear conditioning circuits, including the basolateral and central amygdala, hippocampus as well as downstream effector regions such as the periacqueductal gray (freezing), nucleus reticularis pontis caudalis (potentiated startle), and the lateral (autonomic responses) and paraventricular (hormonal responses) nuclei of the hypothalamus. Thus, CRF₁ pathways are well-positioned to modulate the learning, storage and expression of fear conditioning Figure from (Sotres-Bayon et al., 2006). Reprinted with permission from Elsevier.