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Open AccessArticle

Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala

1
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
2
Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
3
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, USA
*
Author to whom correspondence should be addressed.
Brain Sci. 2019, 9(12), 361; https://doi.org/10.3390/brainsci9120361
Received: 20 November 2019 / Revised: 3 December 2019 / Accepted: 5 December 2019 / Published: 7 December 2019
Myeloid differentiation primary response protein (MyD88) is a critical neuroimmune adaptor protein in TLR (Toll-like receptor) and IL-1R (Interleukin-1 receptor) signaling complexes. These two pro-inflammatory families play an important role in the neurobiology of alcohol use disorder, specifically MyD88 regulates ethanol drinking, ethanol-induced sedation, and ethanol-induced deficits in motor coordination. In this study, we examined the role of MyD88 in mediating the effects of IL-1β and ethanol on GABAergic transmission in the central amygdala (CeA) of male mice using whole-cell patch-clamp recordings in combination with pharmacological (AS-1, a mimetic that prevents MyD88 recruitment by IL-1R) and genetic (Myd88 knockout mice) approaches. We demonstrate through both approaches that IL-1β and ethanol’s modulatory effects at CeA GABA synapses are not dependent on MyD88. Myd88 knockout potentiated IL-1β’s actions in reducing postsynaptic GABAA receptor function. Pharmacological inhibition of MyD88 modulates IL-1β’s action at CeA GABA synapses similar to Myd88 knockout mice. Additionally, ethanol-induced CeA GABA release was greater in Myd88 knockout mice compared to wildtype controls. Thus, MyD88 is not essential to IL-1β or ethanol regulation of CeA GABA synapses but plays a role in modulating the magnitude of their effects, which may be a potential mechanism by which it regulates ethanol-related behaviors. View Full-Text
Keywords: interleukin-1; IL-1R1; neuroimmune; alcohol; Myd88 knockout; sIPSC; GABA interleukin-1; IL-1R1; neuroimmune; alcohol; Myd88 knockout; sIPSC; GABA
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Bajo, M.; Patel, R.R.; Hedges, D.M.; Varodayan, F.P.; Vlkolinsky, R.; Davis, T.D.; Burkart, M.D.; Blednov, Y.A.; Roberto, M. Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala. Brain Sci. 2019, 9, 361.

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