Abstract
Chronic or prolonged exposure to stress ranks among the most important socioenvironmental factors contributing to the development of neuropsychiatric diseases, a process generally associated with loss of inhibitory tone in amygdala. Recent studies have identified distinct neuronal circuits within the basolateral amygdala (BLA) engaged in different emotional processes. However, the potential circuit involved in stress-induced dysregulation of inhibitory tones in BLA remains elusive. Here, a transgenic mouse model expressing yellow fluorescent protein under control of the Thy1 promoter was used to differentiate subpopulations of projection neurons (PNs) within the BLA. We observed that the tonic inhibition in amygdala neurons expressing and not expressing Thy1 (Thy1+/−) was oppositely regulated by chronic social defeat stress (CSDS). In unstressed control mice, the tonic inhibitory currents were significantly stronger in Thy1- PNs than their Thy1+ counterparts. CSDS markedly reduced the currents in Thy1- projection neurons (PNs), but increased that in Thy1+ ones. By contrast, CSDS failed to affect both the phasic A-type γ-aminobutyric acid receptor (GABAAR) currents and GABABR currents in these two PN populations. Moreover, chronic corticosterone administration was sufficient to mimic the effect of CSDS on the tonic inhibition of Thy1+ and Thy1- PNs. As a consequence, the suppression of tonic GABAAR currents on the excitability of Thy1- PNs was weakened by CSDS, but enhanced in Thy1+ PNs. The differential regulation of chronic stress on the tonic inhibition in Thy1+ and Thy1- neurons may orchestrate cell-specific adaptation of amygdala neurons to chronic stress.
Highlights
Exposure to extreme or prolonged stress leads to a spectrum of brain and behavior abnormalities and is associated with the onset and exacerbation of various neuropsychiatric diseases including anxiety disorder and depression (de Kloet et al, 2005; McEwen, 2007)
We have recently observed that the impaired inhibition in amygdala by chronic stress is primarily due to the loss of tonic inhibition (Liu et al, 2014), which is mediated by extrasynaptic GABAARs, rather than the phasic inhibition by synaptic GABAARs
We showed that chronic social defeat stress (CSDS) drastically increased the tonic GABAAR currents in Thy1+ neurons, but decreased the currents in Thy1- ones in basolateral amygdala (BLA)
Summary
Exposure to extreme or prolonged stress leads to a spectrum of brain and behavior abnormalities and is associated with the onset and exacerbation of various neuropsychiatric diseases including anxiety disorder and depression (de Kloet et al, 2005; McEwen, 2007). Amygdala has a highly inhibitory tone, which distinguishes it from its proximal regions (LeDoux, 2007). This provides a brake for amygdala to limit its activation by the neutral information in the environment, avoiding excessive or inappropriate expression of emotion (Quirk and Gehlert, 2003; Jie et al, 2018). Under some adverse conditions such as prolonged exposure to stressful events, the high inhibitory tone is removed, leading to persistent and excessive activation of amygdala (Manzanares et al, 2005; Liu et al, 2014). Understanding the precise mechanisms underlying stressinduced GABAergic disinhibition in amygdala may yield novel targets for prevention and treatment of stress-related neuropsychiatric disorders
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