Tackling CCK/CB1R expressing GABAergic interneurons in BLA for their role in fear extinction

Authors

• O Gunduz-Cinar
• N Crow
• M Xia
• E Van Leer
• M Wilson
• L Zweifel
• N Hajos
• A Holmes

Abstract

Previously, we demonstrated that cortical inputs into BLA are important for extinction learning and that augmented endocannabinoids signal through their presynaptic receptors modulate synaptic plasticity (Gunduz-Cinar et al 2023). However, the precise contribution of increased endocannabinoids on the CB1Rs expressing BLA cholecystokinin (CCK) interneurons are still not known. While CB1Rs are expressed most abundantly on these GABAergic interneurons, it is also known to express on other neurons and astrocytes. Our previous attempt to manipulate these GABAergic interneurons using the CCK-Cre-Dlx-FLpo double transgenic mice (Rovira-Estaban et al 2019) or the intersct viral strategy with a Cre recombinase on the calcium binding protein of CCK/CB1Rs, namely NECAB 2 (Miczan et al 2021) promoter appeared to be not specific to the CB1Rs that are abundant on CCK interneurons, but also a variety of other cells. We are currently exploring another protein (Sncg, gamma synuclein) that is shown to be selectively expressed by CCK-INs (Dudok et al 2021). We are currently using a mouse line with Sncg promoter to target the CCK/CB1Rs and DREADDs for activating or inhibiting the activity of these cells during behavior. Understanding the precise role of the CB1R expressing interneurons will provide us information on input neuron modulation during fear and extinction learning in BLA. The results of this study will guide us in the development of better therapeutic strategies for anxiety and stress related disorders.

Scientific Focus Area: Neuroscience

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