Astrocytes and memory: emerging evidence and a paradigm shift
摘要
In recent years, with the discovery of astrocytes as components of the tripartite synapse and the development of tools for manipulating astrocyte calcium events, learning and memory are no longer considered the exclusive domain of neurons; activation of astrocytes alone can also trigger memory recall. The mnemonic functions of astrocytes have now been demonstrated in the hippocampus, nucleus accumbens, and amygdala, and are mainly manifested during the memory retrieval phase. On the other hand, cooperation between astrocyte-derived gliotransmitters and memory engram neurons is crucial for the formation and consolidation of both short-term and long-term memory. For example, activation of astrocytic calcium signaling and stimulation by endocannabinoids can induce the release of D-serine, ATP/adenosine, and glutamate, which act on GPCR and thereby influence LTD or LTP. Among these molecules, lactate can also function as a signaling molecule to activate downstream memory processes, potentially involving D-serine- and NMDAR-mediated synaptic plasticity. Similarly, α1, α2, and β-adrenergic receptors, which are predominantly expressed in astrocytes, participate in memory in distinct ways across different brain regions. In addition, this review discusses the mechanisms by which astrocytes, as a medium for memory storage, participate in Alzheimer’s disease, addictive behaviors, sleep disorders, depression, and post-traumatic stress disorder, as well as their therapeutic potential. Finally, this review systematically details the challenges and future directions in elucidating the mechanisms by which astrocytes store and process memory at the current stage, which may facilitate the development of novel astrocyte-targeted therapies for cognition-related disorders.
Graphical Abstract