Journal of Multiscale Neuroscience

Stress alters neuroendocrine, autonomic, and behavioral processes to cope well with perceived threats that compromise subjective wellbeing. Just as the perception of risk can change the structure and function of brain circuitry, which may result in enduring behavioral changes. There needs to be a greater understanding of how the brain reacts to stress-related disorders and discern how the adaptation mechanisms of the central nervous system under acute stress, as well as how stress-induced adaptation mechanisms are altered under chronic stress conditions that may induce plasticity-related changes in the brain. During this interaction, the brain becomes more capable of resolving stress in a way that is either adaptive or maladaptive, leaving the most critical deficit in the emotion regulation associated with risk for pathological conditions. The essence of this associated risk involves the reciprocal influence between hypothalamic-pituitary-adrenal function, the relay nucleus within the amygdala reactivation, and the hippocampus as essential structures associated with the forebrain pathways mediating stress-induced hormones, and the gamma-aminobutyric acid neurotransmitter system as key mechanisms of regulating stress. Understanding how related emotional experiences occur on the neural level and their impact on cognition and behavior entail tracing the interaction between the hypothalamic-pituitary-adrenal axis, the hormones released by these structures, and the neuroendocrine system's reactivity to stress. The interaction between threat-sensitive brain circuitry and the neuroendocrine stress system is crucial to understanding how related emotions arise on the neural level and their impact on cognition and behavior. The hypothalamic-pituitary-adrenal axis is critical in regulating the synthesis and release of endocrine hormones through its interactions with these structures, collectively referred to as the stress response. The stress system is described in its anatomy and physiology and connections to other brain areas and endocrine systems. We explore the current evidence linking stress with pathophysiologic mechanisms implicated in stressful conditions affecting the neuronal circuitry between endocrine, metabolic, gastrointestinal, and immune systems. Examining the biopsychological contributions provides a conceptual framework for understanding the emergence of emotions and stress-related behaviors.