The causal role of the amygdala in the autonomic regulation of stress and anxiety

Abstract

Introduction The amygdala is known to play an important role in the limbic system, which regulates fear and anxiety. Differences in fear and anxiety are associated with changes in autonomic system ie breathing, cardiovascular and urinary function. Although the amygdala has been recognized as an important center within the limbic system, it is not known whether it has any direct causal influence on breathing, cardiovascular or urinary functions. Methods We used both cats and rats for this study. In isoflurane anesthetized, vagi intact, spontaneously breathing cats (n= 4) and in urethane anesthetized vagi-intact spontaneously breathing rats (n = 12), we stereotaxically stimulated the the lateral amygdala (LA) and central amygdala (CeA) with excitatory amino acid [EAA, metabotropic glutamic acid (L-Glut, 500 mM, pH 7.4)], and investigated the changes in diaphragm function, thoracic pressure, blood pressure, heart rate and urodynamic control. EAA technique allows for stimulating only the cell bodies and not the axons or fibers of the passage thus enabling localization of specific areas and neuronal circuits within the amygdala and its causal impact on autonomic (respiratory, cardiovascular and urinary) system. Results from the cat studies Respiratory modulation: In the cat, LA generated hyperpnea and tachypnea while CeA induced dyspnea, bradypnea, inspiratory apneusis and double diaphragm breathing pattern. Apneas were never generated from either of the two regions of the amygdala. Cardiovascular modulation: The cardiovascular effects generated from the cat amygdala were varied and did not show specific topography as respiration. Both LA and CeA induced hypertension as well as hypotension. Micturition: In the cat, stimulation of CeA (but not LA) produced micturition. Results from the rat studies EAA stimulation of CeA induced tachypnea and hypertension. Topical stimulation of the CeL portion of the CeA, produced breath-hold. LA did not induce significant respiratory or cardiovascular effects. CeA however produced both hyper and hypotension. Micturition was not produced from either region of the amygdala. Conclusion 1. Lateral and Central amygdala areas produce distinct autonomic modulation which may define its selection associated with stress, fear and/or anxiety. 2. Species differences between cat and rat exists in terms of autonomic circuitry within the amygdala and their causal effects. These results constitute a variety of autonomic indices that can be translated for clinical determination of stress and anxiety disorders including PTSD and panic disorders in humans. Declaration This work was wholly undertaken in the laboratory of HHS at The University of Queensland between 2015-2017 with full ethics approval provided by the university Animal Ethics Care committee. Both HHS and GH were named investigators on the ethics approvals. None of work described here were undertaken at either of the current work designations of HHS or GH. HHS and GH conceived and designed the project, performed the experiments, analyzed primary data and made figure illustrations. GH curated the final data/figure representation in this presentation/poster. Correspondence to Gert Holstege: holstege23@gmail.com