The dangerous stimuli may be potentially dangerous, distal or proximal and the recognition by the animals of each one of these conditions is determinant for the nature of the fear responses. In the present article a parallel with this particular process is drawn taking into account that different fear responses are generated by light, tones and contexts used as conditioned stimuli and by unconditioned stimulation of the dorsal periaqueductal gray (dPAG). In this review we summarize the efforts that have been made to characterize the neural circuits recruited in the organization of defensive reactions to the conditioned and unconditioned aversive stimulations, particularly evidence linking the brain's defense response systems to the concept of fear-stress-anxiety. The dPAG constitute the main neural substrates for the integration of aversive states in response to proximal aversive stimuli. In fact, panic-like behaviors often result when this structure is electrically or chemically stimulated. On the other hand, successful preparatory processes of danger-orientation and preparedness to flee seem to be linked to anxiety. The pre-frontal and cingulate cortex, median raphe nucleus, septum and hippocampus seem to be implicated in the elaboration and organization of these responses. As a working hypothesis, it is advanced that increasing the intensity and proximity of the danger may lead to an emotional shift. When the animals are submitted to this gradual increase in aversiveness there is a switch from the neural circuits responsible for the production of the orientated and organized motor patterns of appropriate defensive response to a conditioned stimulus towards the incomplete and uncoordinated defense responses related to panic attacks. The circuits in the amygdala and the medial hypothalamus responsible for the organization of the defense reaction may well subserve to this switch process.
Fear; Anxiety; Panic; dPAG; medial hypothalamus; Amygdala; Hippocampus
