Michigan Neuroscience Institute, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, United States; Department of Molecular and Integrative Physiology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, United States.
Michigan Neuroscience Institute, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, United States; Department of Molecular and Integrative Physiology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, United States.
Neurobiol Learn Mem. 2020 Sep;173:107230. doi: 10.1016/j.nlm.2020.107230. Epub 2020 May 12.
Over the last two decades there has been significant progress towards understanding the neural substrates that underlie age-related cognitive decline. Although many of the exact molecular and cellular mechanisms have yet to be fully understood, there is consensus that alterations in neuronal calcium homeostasis contribute to age-related deficits in learning and memory. Furthermore, it is thought that the age-related changes in calcium homeostasis are driven, at least in part, by changes in calcium channel expression. In this review, we focus on the role of a specific class of calcium channels: L-type voltage-gated calcium channels (LVGCCs). We provide the reader with a general introduction to voltage-gated calcium channels, followed by a more detailed description of LVGCCs and how they serve to regulate neuronal excitability via the post burst afterhyperpolarization (AHP). We conclude by reviewing studies that link the slow component of the AHP to learning and memory, and discuss how age-related increases in LVGCC expression may underlie cognitive decline by mediating a decrease in neuronal excitability.
在过去的二十年中，人们在理解导致与年龄相关的认知能力下降的神经基础方面取得了重大进展。尽管许多确切的分子和细胞机制尚未完全理解，但人们普遍认为神经元钙稳态的改变导致了与年龄相关的学习和记忆缺陷。此外，人们认为钙稳态的与年龄相关的变化至少部分是由钙通道表达的变化驱动的。在这篇综述中，我们重点介绍了一类特定的钙通道：L 型电压门控钙通道（LVGCCs）。我们为读者提供了一个关于电压门控钙通道的一般介绍，然后更详细地描述了 LVGCCs 以及它们如何通过爆发后超极化（AHP）来调节神经元兴奋性。最后，我们回顾了将 AHP 的慢成分与学习和记忆联系起来的研究，并讨论了与年龄相关的 LVGCC 表达增加如何通过介导神经元兴奋性的降低来导致认知能力下降。
