Stress Response Mechanisms

Overview

This lecture covers the neural and hormonal mechanisms underlying the stress response, focusing on the roles of the autonomic nervous system, HPA axis, feedback regulation, and how stress influences key brain regions and behavior.

Components of the Stress Response

• The stress response is initiated when a threat cue activates the amygdala with input from the hippocampus and prefrontal cortex.
• The amygdala triggers the sympathetic nervous system (SNS) for a rapid fight-or-flight response and the hypothalamus for a slower hormonal (HPA axis) response.
• The SNS releases norepinephrine onto organs and stimulates the adrenal medulla to release epinephrine (adrenaline).
• The HPA axis activation takes minutes and involves sequential hormone release: CRH (hypothalamus) → ACTH (anterior pituitary) → cortisol (adrenal cortex).

Autonomic Nervous System: SNS vs. PNS

• SNS activates fight-or-flight functions: increases heart rate, dilates pupils, inhibits digestion, and releases adrenaline.
• PNS promotes rest-and-digest functions: slows heart rate, constricts pupils, stimulates digestion and salivation.
• Both branches innervate the same organs but have opposing actions.

HPA Axis and Hormonal Control

• The HPA axis links the hypothalamus, pituitary, and adrenal glands to control stress hormone release.
• CRH from the hypothalamus induces ACTH release from the anterior pituitary, which then stimulates cortisol production in the adrenal cortex.
• Cortisol affects many systems: increases blood pressure and glucose, suppresses reproduction and immunity, and influences brain function.

Feedback Mechanisms

• Negative feedback loops regulate the HPA axis to prevent excessive hormone release.
• Cortisol inhibits both the pituitary (reducing ACTH) and hypothalamus (reducing CRH).
• Limbic structures (hippocampus, prefrontal cortex, amygdala) provide additional feedback to modulate the stress response.

Cortisol Receptor Signaling

• Cortisol acts by binding intracellular glucocorticoid receptors (GR) and mineralocorticoid receptors (MR).
• MR have high affinity and are mostly occupied at baseline cortisol; GR are stress-activated and found everywhere in the body.
• The cortisol-GR complex enters the nucleus to regulate gene expression, altering cell function throughout the body.

Brain Regions and Stress

• The amygdala coordinates emotional and physiological responses to stress, potentiates fear learning, and is hyperactive in PTSD.
• The hippocampus inhibits the HPA axis and is involved in memory regulation; chronic stress impairs hippocampal function and neurogenesis.
• The prefrontal cortex (PFC) exerts top-down control, inhibits the amygdala, and is sensitive to dopamine fluctuations during stress.
• The hypothalamus integrates signals for both rapid and hormonal responses, critical for adaptive behaviors and coping.

Recovery and Restoring Balance

• Restoring balance after stress involves SNS deactivation and PNS activation (e.g., via vagus nerve stimulation from deep breathing).
• Cortisol levels may remain elevated for hours even after the initial threat is gone.

Key Terms & Definitions

• Sympathetic Nervous System (SNS) — branch of the ANS mediating rapid fight-or-flight responses.
• Parasympathetic Nervous System (PNS) — branch of the ANS mediating rest-and-digest responses.
• HPA Axis — hypothalamic-pituitary-adrenal axis; hormonal pathway controlling the stress response.
• CRH — corticotropin releasing hormone; released from the hypothalamus to activate the pituitary.
• ACTH — adrenocorticotropic hormone; released from the anterior pituitary to stimulate the adrenal cortex.
• Cortisol — main glucocorticoid stress hormone in humans; modulates metabolism and immune function.
• Glucocorticoid Receptor (GR) — intracellular receptor for cortisol, stress-responsive.
• Mineralocorticoid Receptor (MR) — receptor with high affinity for cortisol, mostly occupied at baseline.
• Negative Feedback — process in which the end product inhibits its own production pathway.

Action Items / Next Steps

• Review diagrams of stress circuitry and feedback loops.
• Read about the roles of the amygdala, hippocampus, and prefrontal cortex in emotional regulation.
• Prepare for discussion or questions on how chronic stress impacts brain function and behavior.