Hijazi Sara, Smit August B, van Kesteren Ronald E
Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK.
Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, 1081 HV, Amsterdam, The Netherlands.
Mol Psychiatry. 2023 Dec;28(12):4954-4967. doi: 10.1038/s41380-023-02168-y. Epub 2023 Jul 7.
Fast-spiking parvalbumin (PV) interneurons are inhibitory interneurons with unique morphological and functional properties that allow them to precisely control local circuitry, brain networks and memory processing. Since the discovery in 1987 that PV is expressed in a subset of fast-spiking GABAergic inhibitory neurons, our knowledge of the complex molecular and physiological properties of these cells has been expanding. In this review, we highlight the specific properties of PV neurons that allow them to fire at high frequency and with high reliability, enabling them to control network oscillations and shape the encoding, consolidation and retrieval of memories. We next discuss multiple studies reporting PV neuron impairment as a critical step in neuronal network dysfunction and cognitive decline in mouse models of Alzheimer's disease (AD). Finally, we propose potential mechanisms underlying PV neuron dysfunction in AD and we argue that early changes in PV neuron activity could be a causal step in AD-associated network and memory impairment and a significant contributor to disease pathogenesis.
快速发放小白蛋白(PV)中间神经元是具有独特形态和功能特性的抑制性中间神经元,这些特性使它们能够精确控制局部神经回路、脑网络和记忆处理。自1987年发现PV在一部分快速发放的γ-氨基丁酸(GABA)能抑制性神经元中表达以来,我们对这些细胞复杂的分子和生理特性的了解一直在不断扩展。在这篇综述中,我们强调了PV神经元的特定特性,这些特性使它们能够高频且可靠地发放,从而能够控制网络振荡并塑造记忆的编码、巩固和提取。接下来,我们讨论多项研究,这些研究报告称在阿尔茨海默病(AD)小鼠模型中,PV神经元损伤是神经网络功能障碍和认知衰退的关键步骤。最后,我们提出了AD中PV神经元功能障碍的潜在机制,并认为PV神经元活动的早期变化可能是AD相关网络和记忆损伤的一个因果步骤,也是疾病发病机制的一个重要因素。