The Effect Of Chronic Stress On The Tonic Inhibitory Current In Lateral Amygdala

As a key part of the limbic system in the mammalian brain, the amygdala complex plays an essential role in the generation and expression of emotion such as fear and anxiety. As generally known, chronic stress exposure leads to the overexcitation of the projection neurons in amygdala, resulting in long-lasting and inappropriate expression of anxiety. However, the underpinning neurobiological mechanisms remain largely unknown. Here, we make two mice models to mimic the chronic stress exposure in reality-chronic immobilization stress (CIS) and chronic unpredictable stress (CUS). By using the whole-cell configuration of patch clamp in amygdala slices, we investigate the possible influence of CIS and CUS on the inhibitory current of the projection neurons in amygdala. We find both forms of chronic stress conspicuously decrease the tonic inhibitory currents in the PNs, which are mediated by the GABAA receptors (GABAARs) in extrasynaptic membrane. By contrast, they have only negligible effect on the phasic inhibitory currents mediated by the postsynaptic GABAARs. Such effect is largely dependent on the time course of CIS. While CIS for8-10days significantly compromises the tonic inhibitory currents in PNs, CIS for4-6days has only slight but insignificant influence on tonic currents. Further study demonstrates that the CIS-evoked loss of tonic inhibitory current is primarily mediated by the activation glucocorticoid receptors. Feeding the mice with5μM corticosterone (CORT) mimics the effect of chronic stress on tonic inhibition and strikingly suppresses the tonic inhibitory currents in amygdala PNs. Moreover, pretreatment of the CIS mice with glucocorticoid receptor antagonist RU38486completely reverses the loss of tonic inhibitory currents. By contrast, mineralocorticoid receptor antagonist spironolactone has no effect on the decreased tonic inhibition. Thus, our study offers important experimental evidence to unveil the neurobiological basis underlying the action of CIS on amygdala and provides potential target for the prevention and treatment of mental disorders such as anxiety disorders.