Chronic Stress Causes Amygdala Hyperexcitability in Rodents

• Published in: Biological psychiatry (1969) 2010-06, Vol.67 (12), p.1128-1136
• Main Authors: Rosenkranz, J. Amiel, Venheim, Emily R, Padival, Mallika
• Format: Article
• Language: English
• Subjects: Action Potentials - physiology; Adrenal Glands - physiopathology; Adult and adolescent clinical studies; Amygdala; Amygdala - drug effects; Amygdala - physiopathology; Animals; Biological and medical sciences; Calcium Channel Agonists - pharmacology; Calcium Channel Blockers - pharmacology; Chronic Disease; chronic stress; Depression; in vivo intracellular electrophysiology; Male; Maze Learning - physiology; Medical sciences; membrane properties; Mood disorders; neuronal activity; Neurons - drug effects; Neurons - physiology; Potassium Channel Blockers - pharmacology; Potassium Channels, Calcium-Activated - agonists; Potassium Channels, Calcium-Activated - antagonists & inhibitors; Potassium Channels, Calcium-Activated - physiology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; Stilbenes - pharmacology; Stress, Psychological - physiopathology
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2010.02.008

Background Chronic stress is a major health concern, often leading to depression, anxiety, or when severe enough, posttraumatic stress disorder. While many studies demonstrate that the amygdala is hyperresponsive in patients with these disorders, the cellular neurophysiological effects of chronic stress on the systems that underlie psychiatric disorders, such as the amygdala, are relatively unknown. Methods In this study, we examined the effects of chronic stress on the activity and excitability of amygdala neurons in vivo in rats. We used in vivo intracellular recordings from single neurons of the lateral amygdala (LAT) to measure neuronal properties and determine the cellular mechanism for the effects of chronic stress on LAT neurons. Results We found a mechanism for the effects of chronic stress on amygdala activity, specifically that chronic stress increased excitability of LAT pyramidal neurons recorded in vivo. This hyperexcitability was caused by a reduction of a regulatory influence during action potential firing, facilitating LAT neuronal activity. The effects of stress on excitability were occluded by agents that block calcium-activated potassium channels and reversed by pharmacological enhancement of calcium-activated potassium channels. Conclusions These data demonstrate a specific channelopathy that occurs in the amygdala after chronic stress. This enhanced excitability of amygdala neurons after chronic stress may explain the observed hyperresponsiveness of the amygdala in patients with posttraumatic stress disorder and may facilitate the emergence of depression or anxiety in other patients.