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Alterations in Intrinsic and Synaptic Properties of Hippocampal CA1 VIP Interneurons During Aging
Frontiers in Cellular Neuroscience ( IF 5.3 ) Pub Date : 2020-09-10 , DOI: 10.3389/fncel.2020.554405
Ruggiero Francavilla , Alexandre Guet-McCreight , Sona Amalyan , Chin Wai Hui , Dimitry Topolnik , Félix Michaud , Beatrice Marino , Marie-Ève Tremblay , Frances K. Skinner , Lisa Topolnik

Learning and memory deficits are hallmarks of the aging brain, with cortical neuronal circuits representing the main target in cognitive deterioration. While GABAergic inhibitory and disinhibitory circuits are critical in supporting cognitive processes, their roles in age-related cognitive decline remain largely unknown. Here, we examined the morphological and physiological properties of the hippocampal CA1 vasoactive intestinal peptide/calretinin-expressing (VIP+/CR+) type 3 interneuron-specific (I-S3) cells across mouse lifespan. Our data showed that while the number and morphological features of I-S3 cells remained unchanged, their firing and synaptic properties were significantly altered in old animals. In particular, the action potential duration and the level of steady-state depolarization were significantly increased in old animals in parallel with a significant decrease in the maximal firing frequency. Reducing the fast-delayed rectifier potassium or transient sodium conductances in I-S3 cell computational models could reproduce the age-related changes in I-S3 cell firing properties. However, experimental data revealed no difference in the activation properties of the Kv3.1 and A-type potassium currents, indicating that transient sodium together with other ion conductances may be responsible for the observed phenomena. Furthermore, I-S3 cells in aged mice received a stronger inhibitory drive due to concomitant increase in the amplitude and frequency of spontaneous inhibitory currents. These age-associated changes in the I-S3 cell properties occurred in parallel with an increased inhibition of their target interneurons and were associated with spatial memory deficits and increased anxiety. Taken together, these data indicate that VIP+/CR+ interneurons responsible for local circuit disinhibition survive during aging but exhibit significantly altered physiological properties, which may result in the increased inhibition of hippocampal interneurons and distorted mnemonic functions.



中文翻译:

在衰老过程中海马CA1 VIP内部神经元的内在和突触特性的变化。

学习和记忆障碍是大脑衰老的标志,皮质神经元回路代表认知退化的主要目标。尽管GABA能抑制和去抑制回路在支持认知过程中至关重要,但它们在与年龄相关的认知能力下降中的作用仍然未知。在这里,我们检查了小鼠整个寿命期间海马CA1血管活性肠肽/钙调蛋白表达(VIP + / CR +)3型神经元特异性(I-S3)细胞的形态和生理特性。我们的数据显示,虽然I-S3细胞的数量和形态特征保持不变,但它们的放电和突触特性在老年动物中已显着改变。尤其是,老年动物的动作电位持续时间和稳态去极化水平显着增加,同时最大发射频率显着下降。在I-S3细胞计算模型中减少快速延迟的整流器钾或瞬态钠电导可以重现与年龄相关的I-S3细胞放电特性变化。但是,实验数据表明Kv3.1和A型钾电流的激活特性没有差异,这表明瞬态钠和其他离子电导可能是所观察到的现象的原因。此外,由于自发抑制电流的幅度和频率的同时增加,老年小鼠的I-S3细胞受到更强的抑制作用。I-S3细胞特性的这些与年龄相关的变化与对其靶标中神经元的抑制作用增加同时发生,并与空间记忆缺陷和焦虑增加有关。综上所述,这些数据表明,负责局部回路抑制的VIP + / CR +中间神经元在衰老过程中可以存活,但表现出显着改变的生理特性,这可能导致海马中间神经元的抑制作用增强和记忆功能失真。

更新日期:2020-10-15
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