MPP2 Interacts with SK2 to Rescue the Excitability of Glutamatergic Neurons in the BLA and Facilitate the Extinction of Conditioned Fear in Mice

Overview

Journal CNS Neurosci Ther

Specialties Neurology
Pharmacology

Date 2023 Jul 20

PMID 37469037

Authors

Xiaohan Peng

Panpan Chen

Yang Zhang

Ke Wu

Ningning Ji

Jinghua Gao

Hui Wang

Yong-Mei Zhang

Tie Xu

Rong Hua

Affiliations

Soon will be listed here.

Abstract

Aims: The basolateral amygdala (BLA) plays an integral role in anxiety disorders (such as post traumatic stress disorder) stem from dysregulated fear memory. The excitability of glutamatergic neurons in the BLA correlates with fear memory, and the afterhyperpolarization current (I ) mediated by small-conductance calcium-activated potassium channel subtype 2 (SK2) dominates the excitability of glutamatergicneurons. This study aimed to explore the effect of MPP2 interacts with SK2 in the excitability of glutamatergic neurons in the BLA and the extinction of conditioned fear in mice.

Methods: Fear memory was analyzed via freezing percentage. Western blotting and fluorescence quantitative PCR were used to determine the expression of protein and mRNA respectively. Electrophysiology was employed to measure the excitability of glutamatergic neurons and I .

Results: Fear conditioning decreased the levels of synaptic SK2 channels in the BLA, which were restored following fear extinction. Notably, reduced expression of synaptic SK2 channels in the BLA during fear conditioning was caused by the increased activity of protein kinase A (PKA), while increased levels of synaptic SK2 channels in the BLA during fear extinction were mediated by interactions with membrane-palmitoylated protein 2 (MPP2).

Conclusions: Our results revealed that MPP2 interacts with the SK2 channels and rescues the excitability of glutamatergic neurons by increasing the expression of synaptic SK2 channels in the BLA to promote the normalization of anxiety disorders and provide a new direction for the treatment.

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MPP2 interacts with SK2 to rescue the excitability of glutamatergic neurons in the BLA and facilitate the extinction of conditioned fear in mice.

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