Erofeev Alexander, Vinokurov Egor, Bol'shakova Anastasia, Bezprozvanny Ilya, Vlasova Olga
Laboratory of Molecular Neurodegeneration, Graduate School of Biomedical Systems and Technologies, Institute of Biomedical Systems and Biotechnology, Peter the Great St. Petersburg Polytechnic University, Saint Petersburg, Russia.
Laboratory of Molecular Neurobiology, Pavlov Institute of Physiology, Russian Academy of Sciences, Saint Petersburg, Russia.
Front Aging Neurosci. 2025 Aug 20;17:1550673. doi: 10.3389/fnagi.2025.1550673. eCollection 2025.
Alzheimer's disease (AD) is a neurodegenerative disorder that leads to progressive cognitive decline and significant disruptions in hippocampal neural networks, critically impacting memory and learning. Understanding the neural mechanisms underlying these impairments is essential for developing effective therapies. The 5xFAD mouse model, known for progressive neurodegeneration and cognitive deficits, provides a valuable platform for investigating associative learning and memory impairments related to AD. However, the electrophysiological state of the hippocampal alveus in 5xFAD mice during learning and memory formation remains poorly understood. Here, we performed one-photon calcium imaging of CA1 hippocampal neurons with wireless electrophysiological recordings from the hippocampal alveus in freely moving 5xFAD mice to explore specific neural alterations during a fear conditioning test. Our results demonstrate significant deficits in the learning and memory capacities of 5xFAD mice, showing impairments in hippocampal-dependent contextual and tone-associated memory retrieval, along with disrupted calcium dynamics and impaired electrophysiological activity in the hippocampal alveus. These findings reveal patterns of network dysregulation associated with AD. These findings enhance our understanding of the specific neural dysfunctions contributing to the cognitive decline associated with memory loss in AD and emphasize the value of applying methods to elucidate neurodegenerative mechanisms. This approach provides a foundation for future studies on AD pathophysiology and may inform the development of targeted therapeutic strategies to mitigate memory impairments in AD.
阿尔茨海默病(AD)是一种神经退行性疾病,会导致认知功能逐渐衰退,并严重破坏海马神经网络,对记忆和学习产生重大影响。了解这些损伤背后的神经机制对于开发有效的治疗方法至关重要。5xFAD小鼠模型以进行性神经退行性变和认知缺陷而闻名,为研究与AD相关的联想学习和记忆损伤提供了一个有价值的平台。然而,5xFAD小鼠在学习和记忆形成过程中海马齿状回的电生理状态仍知之甚少。在这里,我们对自由活动的5xFAD小鼠的海马CA1神经元进行了单光子钙成像,并同时记录了海马齿状回的无线电生理信号,以探索恐惧条件反射测试期间的特定神经变化。我们的结果表明,5xFAD小鼠在学习和记忆能力方面存在显著缺陷,表现为海马依赖性情境记忆和音调相关记忆检索受损,同时海马齿状回的钙动力学紊乱和电生理活动受损。这些发现揭示了与AD相关的网络失调模式。这些发现加深了我们对导致AD记忆丧失相关认知衰退的特定神经功能障碍的理解,并强调了应用方法阐明神经退行性机制的价值。这种方法为未来AD病理生理学研究奠定了基础,并可能为开发减轻AD记忆损伤的靶向治疗策略提供参考。