NPTX2 transfection improves synaptic E/I balance and performance in learning impaired aged rats

IF 6.1 2区医学 Q1 NEUROSCIENCES

Progress in Neurobiology Pub Date : 2025-03-07 DOI:10.1016/j.pneurobio.2025.102746

Daniel Severin , Ming Teng Koh , Cristian Moreno , Darwin Contreras , Altagracia Contreras , Christian Wesselborg , Michelle Bridi , Jala Atufa , Audrey Branch , Paul Worley , Michela Gallagher , Alfredo Kirkwood

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Abstract

Excessive neural activity in the medial temporal lobe commonly associates with cognitive decline in elderly humans and also in rodents.An attractive model pathway to study synaptic mechanisms underlying age-dependent circuit hyperexcitability is the connection made by lateral entorhinal cortex cells onto the dentate gyrus (LEC→DG). Both structures are particularly affected by age and, importantly, in behaviorally characterized aged rats, learning impairment correlates with diminished feedforward inhibition of granule cells recruited by LEC inputs. In this rat model of aging, we evaluated how overexpression of Neuronal Pentraxin 2 (NPTX2) in the LEC, essential for stabilizing excitatory inputs onto fast-spiking inhibitory interneurons (FS-INs), enhances feedforward inhibition and improves spatial memory in impaired individuals. In addition, we found that FS-INs from unimpaired aged individuals have an increased excitatory drive compared to young individuals. These findings support the notion that NPTX2-mediated compensatory mechanisms to enhance the recruitment of FS-INs are crucial to maintaining proficient memory performance during aging.

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NPTX2转染改善老年学习障碍大鼠突触E/I平衡和表现。

过度的内侧颞叶神经活动通常与老年人和啮齿动物的认知能力下降有关。研究年龄依赖性神经回路高兴奋性突触机制的一个有吸引力的模型途径是侧鼻内皮层细胞与齿状回（LEC→DG）的连接。这两种结构都特别受年龄的影响，重要的是，在行为特征明显的老年大鼠中，学习障碍与LEC输入募集的颗粒细胞前馈抑制减弱有关。在这个大鼠衰老模型中，我们评估了LEC中神经元戊烯酮2 （NPTX2）的过度表达如何增强前馈抑制并改善受损个体的空间记忆，这对于稳定对快速抑制中间神经元（fos - ins）的兴奋输入至关重要。此外，我们发现，与年轻人相比，来自未受损老年人的FS-INs具有更高的兴奋驱动。这些发现支持了nptx2介导的代偿机制增强FS-INs的招募对于在衰老过程中保持熟练的记忆表现至关重要的观点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Progress in Neurobiology 医学-神经科学

CiteScore

12.80

自引率

1.50%

发文量

107

审稿时长

33 days

期刊介绍： Progress in Neurobiology is an international journal that publishes groundbreaking original research, comprehensive review articles and opinion pieces written by leading researchers. The journal welcomes contributions from the broad field of neuroscience that apply neurophysiological, biochemical, pharmacological, molecular biological, anatomical, computational and behavioral analyses to problems of molecular, cellular, developmental, systems, and clinical neuroscience.