The brain structures that constitute a neural circuit of fear and anxiety should have the following features:
1. There is sufficient afferent sensory input to permit assessment of the fear- or anxiety-provoking nature of the external threat or internal stress.
2. Neural interactions among the brain structures capable of incorporating an individual's prior experience or memory into the appraisal of stimuli. These interactions are important in the attachment of affective significance to specific stimuli and the mobilization of adaptive behavioral responses.
3. Efferent projections from the brain structures should be able to mediate an individual's neuroendocrine, autonomic, and motor response to threat as well account for the pathological reactions that result in anxiety-related signs and symptoms.
To underscore its survival importance, many brain areas with redundant circuits are involved to subserve this important constellation of behaviors. Critical brain structures capable of incorporating an individual's prior experience or memory into the appraisal of stimuli are amygdala, LC, hippocampus, thalamus, hypothalamus, periaqueductal grey (PAG), and pre-frontal cortex. Alterations in neurochemical and neurotransmitter systems that mediate the stress response also play a role in anxiety. Important neurotransmitters are corticotrophine-releasing factor (CRF), adrenocorticotrophic hormone (ACTH), norepinephrine (NE), epinephrine, dopamine, cortisol, benzodiazepines (Bzs), opioids, and other neurochem-ical systems.
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