The host of physiological changes activated by a stressful event are unleashed in part by activation of a nucleus in the brain stem called the locus ceruleus. This nucleus is the origin of most norepinephrine pathways in the brain. Neurons using norepinephrine as their neurotransmitter project bilaterally from the locus ceruleus along distinct pathways to the cerebral cortex, limbic system, and the spinal cord, among other projections.
Normally, when someone is in a serene, unstimulated state, the "firing" of neurons in the locus ceruleus is minimal. A novel stimulus, once perceived, is relayed from the sensory cortex of the brain through the thalamus to the brain stem. That route of signaling increases the rate of noradrenergic activity in the locus ceruleus, and the person becomes alert and attentive to the environment. If the stimulus is perceived as a threat, a more intense and prolonged discharge of the locus ceruleus activates the sympathetic division of the autonomic nervous system (Thase & Howland, 1995). The activation of the sympathetic nervous system leads to the release of norepinephrine from nerve endings acting on the heart, blood vessels, respiratory centers, and other sites. The ensuing physiological changes constitute a major part of the acute stress response. The other major player in the acute stress response is the hypothalamic-pituitary-adrenal axis.