Spontaneous activity of astrocytes is a stochastic functional signal for memory consolidation

• 成果类型: Article
• 署名作者: Losi, Gabriele; Vignoli, Beatrice; Granata, Rocco; Lia, Annamaria; Zonta, Micaela; Sansevero, Gabriele; Pischedda, Francesca; Chiavegato, Angela; Santi, Spartaco; Zentilin, Lorena; Berardi, Nicoletta; Ratto, Gian Michele; Carmignoto, Giorgio; Canossa, Marco
• 署名单位: Consiglio Nazionale delle Ricerche (CNR); University of Padua; University of Trento; University of Trento; Scuola Normale Superiore di Pisa; University of Padua; Consiglio Nazionale delle Ricerche (CNR); Istituto di Neuroscienze (IN-CNR); Consiglio Nazionale delle Ricerche (CNR); IRCCS Istituto Ortopedico Rizzoli; International Center for Genetic Engineering & Biotechnology (ICGEB); University of Florence; Consiglio Nazionale delle Ricerche (CNR); Istituto di Biofisica (IBF-CNR); Consiglio Nazionale delle Ricerche (CNR); Istituto Nanoscienze (NANO-CNR); European Academy of Bozen-Bolzano
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2500511122
• 发表日期: 2025-10-21
• 页码: e2500511122
• 关键词: neurotrophins; Ca2+microdomains; memory circuits; synaptic plasticity; long-term potentiation; CALCIUM OSCILLATIONS; glia; stabilization; DEPRESSION; transients; allocation; secretion; mechanism; neurons

摘要

In the absence of explicit neuronal inputs, the glial cell astrocytes exhibit recurring intracellular Ca2+ fluctuations, primarily localized at thin processes, known as Ca2+ microdomains (MDs). Although spontaneous Ca2+ MDs are present throughout the brain, their putative role is unknown. Here, we question whether, owing to their recurring signaling mode, spontaneous Ca2+ MDs contribute to slowly evolving phenomena in the brain, such as memory consolidation. We demonstrate that, in the perirhinal cortex, a central region in recognition memory, these events promote Ca2+- dependent gliotransmission and modulate synaptic strengthening. Their recurring activity extends the release of the gliotransmitter brain- derived neurotrophic factor (BDNF) over time, ensuring the sustained Tropomyosin Receptor Kinase B (TrkB)- signaling required for the consolidation of long- term synaptic potentiation and lasting memories. We also show that Ca2+ MDs, which are stochastic events, preserve their random behavior during gliotransmission, introducing an element of unpredictability into the process of memory retention. Our study assigns to spontaneous, stochastic activity in astrocytes a unique functional role in shaping and stabilizing memory circuits.