Altered inhibitory function in hippocampal CA2 contributes in social memory deficits in Alzheimer's mouse model

海马 CA2 抑制功能的改变导致阿尔茨海默病小鼠模型出现社交记忆缺陷

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作者:Christophe Clément Rey, Vincent Robert, Guillaume Bouisset, Maïthé Loisy, Sébastien Lopez, Vanessa Cattaud, Camille Lejards, Rebecca Ann Piskorowski, Claire Rampon, Vivien Chevaleyre, Laure Verret

Abstract

Parvalbumin (PV)-expressing interneurons which are often associated with the specific extracellular matrix perineuronal net (PNN) play a critical role in the alteration of brain activity and memory performance in Alzheimer's disease (AD). The integrity of these neurons is crucial for normal functioning of the hippocampal subfield CA2, and hence, social memory formation. Here, we find that social memory deficits of mouse models of AD are associated with decreased presence of PNN around PV cells and long-term synaptic plasticity in area CA2. Furthermore, single local injection of the growth factor neuregulin-1 (NRG1) is sufficient to restore both PV/PNN levels and social memory performance of these mice. Thus, the PV/PNN disruption in area CA2 could play a causal role in social memory deficits of AD mice, and activating PV cell pro-maturation pathways may be sufficient to restore social memory.

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