The importance of brainstem mechanisms in the neurobiology of stress and anxiety

Abstract

The medial hypothalamus, amygdala, and dorsal periaqueductal gray (dPAG) constitute the main neural substrates for the integration of aversive states in the brain. In fact, fear-like behaviors often result when these sites are electrically or chemically stimulated. We report here that different fear responses are generated by light, tones and contexts used as conditioned stimuli as well as by unconditioned stimulation of the dPAG. Recent data from this laboratory are also presented showing the influence of past experience with stressful situations on the performance of animals in the fear-potentiated startle and contextual fear procedure. Efforts have been made to characterize the neural circuits recruited in the organization of defensive reactions to these conditioned and unconditioned aversive stimulations. In this review we summarize the evidence linking the brain's defense response systems to the concept of fearstress-anxiety. Successful preparatory processes of danger-orientation and preparedness to flee seem to be linked to anxiety. On the other hand, fear stimuli that originate active but incomplete forms of defensive response ensure emotional states of a different nature. As a working hypothesis, it is advanced that past experience with stressors may lead to this emotional shift. When these animals are submitted to a contextual conditioning procedure there is a switch from the neural circuits responsible for the production of the usual defensive response to an aversive context towards thwarted defense responses related to panic attacks. Therefore, prior experience with stressor events may thwart instinctive, orientated and organized motor patterns of appropriate defensive behaviors to contextual aversive stimuli and result in incomplete and uncoordinated motor acts. This switch process may have the ventral PAG medial hypothalamus-dorsal PAG circuit as its underlying neural substrate.