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Perineuronal nets protect long-term memory by limiting activi
chTEA and eArch viruses (From BrainVTA) were used for optogenetic manipulation to specifically activate and inactivate the PV interneurons respectively.
The viruses used in this article from BrainVTA are in the table below
Control  PT-0258 pAAV-EF1a-dio-EGFP
Optogenetic  PT-0633 pAAV-dio-Arch3-EGFP
 PT-0232 AAV-EF1a-DIO-chTEA -YFP-WPRE
 pAAV-CaMKII-oChief
 pAAV-CaMKII-eArch3
Pub Date: 2019-12-15, DOI: 10.1073/pnas.1902680116   Email: [email protected]
Wei Shi, Xiangbo Wei, Xiaofei Wang, Shuwen Du, Weixuan Liu, Jian Song, and Yun Wang
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.

Fig.1 Optogenetic manipulation of PV interneurons and PNN on fear memory consolidation.
To study the effects of PNNs on contextual fear memory, using behavioral, electrophysiological, and optogenetic (From BrainVTA) approaches to revel the role of PNNs in fear memory consolidation and reconsolidation and GABAergic long-term potentiation (LTP), the results reveal the important contribution of hippocampal and cortical PNNs to contextual fear memories by regulating feedback inhibition of PV interneurons.
 
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