Astrocytes play a critical role in mediating the effect of acute ethanol on central amygdala glutamatergic transmission

Subregional Differences in Alcohol Modulation of Central Amygdala Neurocircuitry

“…A study by explored the effect of alcohol on the CeA L in alcohol naive male C57Bl6/J mice and saw an increase in presynaptic glutamatergic activity after acute alcohol application (5-100 mM) with an estimated IC50 of roughly 20 mM. Expanding on these findings, a recent study from our lab showed that acute bath application of 20 mM alcohol increased spontaneous action potential dependent glutamatergic signaling presynaptically in both male and female C57Bl/6J mice, with no sex differences found (Melkumyan et al, 2022). Additionally, the ability of acute alcohol to increase glutamatergic transmission was attenuated when astrocytes were inhibited either pharmacologically or chemogenetically, suggesting a critical role for astrocytes in the effect of alcohol on CeA L glutamatergic transmission (Melkumyan et al, 2022).…”

“…Most neurons in the CeA are GABAergic, including both GABAergic projection neurons and local interneurons. Overall, studies show that acute alcohol application increases GABAergic transmission in the CeA M , decreases glutamatergic transmission in the CeA M , and increases spontaneous glutamatergic transmission in the CeA L (see further sections below, Roberto, 2004;Roberto et al, 2020;Melkumyan et al, 2022). The concentration of acute bath alcohol application has been extensively studied through concentration response curves in alcohol naïve rodents (see Roberto et al, 2004; showing the apparent IC50 at physiologically relevant concentrations of roughly 20 mM (∼0.092% blood ethanol concentration) for both glutamatergic neurotransmission in mice and GABAergic neurotransmission in rats (Roberto et al, 2004).…”

“…Mediates the mechanism of acute and chronic alcohol on glutamatergic transmission in the CeA (Kisby et al, 2021;Melkumyan et al, 2022) Microglia Mediates the mechanism of chronic alcohol on glutamatergic and GABAergic transmission in the CeA with no effect on alcohol drinking (Warden et al, 2020(Warden et al, , 2021Nelson et al, 2021) Pro-inflammatory cytokines Pro-inflammatory cytokines generally increase CeA GABAergic transmission;…”

“…As the CeA contains heterogeneous subregions, alcohol effects on CeA subregion neurocircuits are also heterogenous. For instance, some studies show an increase in glutamatergic transmission in the lateral subregion of the CeA following acute alcohol ( Silberman et al, 2015 ; Melkumyan et al, 2022 ), other studies show a decrease in glutamatergic transmission in the medial CeA ( Roberto, 2004 ; Herman et al, 2016 ). To better understand the role of the CeA in the development and maintenance of AUD, it is important to parse out the subregional differences on alcohol’s effects on CeA GABAergic and glutamatergic transmission.…”

“…Since CeA L provides direct GABAergic projections to the CeA M , it is proposed that alcohol-induced increase in glutamatergic signaling in the CeA L may directly lead to the well-established alcohol-enhancement of GABA release in the CeA M . Recent findings indicate the acute alcohol-induced increase in glutamatergic transmission in the CeA L is mediated by astrocytes, with potential microglial mediation ( Melkumyan et al, 2022 ), and additional findings indicate that microglia may be critical regulators of CeA GABA transmission in chronic alcohol exposure models ( Warden et al, 2020 ), suggesting neuroimmune signaling in general may be a critical component of alcohol action in the CeA. The effect of alcohol on GABAergic transmission in the CeA L is currently unknown.…”