de León-López Cristina A Muñoz, Carretero-Rey Marta, Khan Zafar U
Laboratory of Neurobiology, Centro de Investigaciones Medico Sanitarias (CIMES), University of Malaga, Calle Marqués de Beccaria, 3, Campus Teatinos s/n, 29010, Malaga, Spain.
Department of Medicine, Faculty of Medicine, University of Malaga, Campus Teatinos s/n, Malaga, Spain.
Cell Mol Neurobiol. 2025 Jan 22;45(1):14. doi: 10.1007/s10571-024-01529-7.
Tetrameric AMPA-type ionotropic glutamate receptors are primary transducers of fast excitatory synaptic transmission in the central nervous system, and their properties and abundance at the synaptic surface are crucial determinants of synaptic efficacy in neuronal communication across the brain. The induction of long-term potentiation (LTP) leads to the insertion of GluA1-containing AMPA receptors at the synaptic surface, whereas during long-term depression (LTD), these receptors are internalized into the cytoplasm of the spine. Disruptions in the trafficking of AMPA receptors to and from the synaptic surface attenuate both forms of synaptic plasticity. Homeostatic scaling up and scaling down, which are additional types of plasticity similar to LTP and LTD, are also regulated by the insertion and removal of GluA1-containing AMPA receptors from the synaptic surface. The trafficking of AMPA receptors is an intricate process assisted by various proteins. Furthermore, AMPA receptors are critical for the formation and consolidation of various types of memory, and alterations in their function are intimately associated with cognitive dysfunction in aging and several neurological and psychiatric diseases. In this review, we will provide an overview of the current understanding of how AMPA receptors regulate various forms of synaptic plasticity, their contribution to memory functions, and their role in aging and brain diseases.
四聚体AMPA型离子型谷氨酸受体是中枢神经系统中快速兴奋性突触传递的主要转导分子，它们在突触表面的特性和丰度是大脑神经元通信中突触效能的关键决定因素。长时程增强（LTP）的诱导导致含GluA1的AMPA受体插入突触表面，而在长时程抑制（LTD）期间，这些受体被内化到树突棘的细胞质中。AMPA受体往返突触表面的运输过程受到破坏会减弱这两种形式的突触可塑性。稳态放大和缩小是与LTP和LTD类似的另外两种可塑性类型，它们也受到突触表面含GluA1的AMPA受体的插入和移除的调节。AMPA受体的运输是一个由多种蛋白质辅助的复杂过程。此外，AMPA受体对各种类型记忆的形成和巩固至关重要，其功能改变与衰老以及几种神经和精神疾病中的认知功能障碍密切相关。在这篇综述中，我们将概述目前对AMPA受体如何调节各种形式的突触可塑性、它们对记忆功能的贡献以及它们在衰老和脑部疾病中的作用的理解。
