Perineuronal nets protect long-term memory by limiting activity-dependent inhibition from parvalbumin interneurons-猫眼课题宝

神经周围网通过限制小白蛋白中间神经元的活动依赖性抑制来保护长期记忆

DOI：

10.1073/pnas.1902680116

发表时间：

2019-12

期刊：

Proceedings of the National Academy of Sciences of the United States of America

影响因子：

11.1

通讯作者：

中科院分区：

综合性期刊1区

文献类型：

作者：

Shi Wei;Wei Xiangbo;Wang Xiaofei;Du Shuwen;Liu Weixuan;Song Jian;Wang Yun

Significance This study reveals the roles of PV interneurons surrounding perineuronal nets (PNNs) in both the hippocampus and the anterior cingulate cortex (ACC) in contextual fear memory. We show that increasing PNN expression in these 2 brain structures enhances the recall and reconsolidation of both recent and remote fear memory, corresponding to the enhancement of GABA-related theta oscillations. Conversely, removal of PNNs impairs consolidation and reconsolidation of both recent and remote fear memory via increased feedback inhibition and impairment of theta oscillations. Together, our results suggest that PNNs in the hippocampus and ACC affect behavioral plasticity during the consolidation and reconsolidation of contextual fear memory by regulating feedback inhibition of PV interneurons. Perineuronal nets (PNNs), a complex of extracellular matrix molecules that mostly surround GABAergic neurons in various brain regions, play a critical role in synaptic plasticity. The function and cellular mechanisms of PNNs in memory consolidation and reconsolidation processes are still not well understood. We hypothesized that PNNs protect long-term memory by limiting feedback inhibition from parvalbumin (PV) interneurons to projection neurons. Using behavioral, electrophysiological, and optogenetic approaches, we investigated the role of PNNs in fear memory consolidation and reconsolidation and GABAergic long-term potentiation (LTP). We made the discovery that the formation of PNNs was promoted by memory events in the hippocampus (HP), and we also demonstrated that PNN formation in both the HP and the anterior cingulate cortex (ACC) is essential for memory consolidation and reconsolidation of recent and remote memories. Removal of PNNs resulted in evident LTP impairments, which were rescued by acute application of picrotoxin, a GABAA receptor blocker, indicating that enhanced inhibition was the cause of the LTP impairments induced by PNN removal. Moreover, removal of PNNs switched GABAA receptor-mediated long-term depression to LTP through a presynaptic mechanism. Furthermore, the reduced activity of PV interneurons surrounded by PNNs regulated theta oscillations during fear memory consolidation. Finally, optogenetically suppressing PV interneurons rescued the memory impairment caused by removal of PNNs. Altogether, these results unveil the function of PV interneurons surrounding PNNs in protecting recent and remote contextual memory through the regulation of PV neuron GABA release.