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

In the absence of explicit neuronal inputs, the glial cell astrocytes exhibit recurring intracellular Ca<sup>2+</sup> fluctuations, primarily localized at thin processes, known as Ca<sup>2+</sup> microdomains (MDs). Although spontaneous Ca<sup>2+</sup> MDs are present throughout the brain, their putative role is unknown. Here, we question whether, owing to their recurring signaling mode, spontaneous Ca<sup>2+</sup> 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 Ca<sup>2+</sup>-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 Ca<sup>2+</sup> 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.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-10-14
DOI
https://doi.org/10.1073/pnas.2500511122
Citations
3
Primary Topic
Neuroinflammation and Neurodegeneration Mechanisms
Type
article
Field-Weighted Citation Impact
2.53
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article

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

Giorgio Carmignoto, Annamaria Lia, Gian Michele Ratto, Francesca Pischedda et al.
3 citations
Proceedings of the National Academy of Sciences
Neuroinflammation and Neurodegeneration Mechanisms
2.53
article

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

Giorgio Carmignoto, Annamaria Lia, Gian Michele Ratto, Francesca Pischedda, Spartaco Santi, Gabriele Losi, Micaela Zonta, R. Granata, Gabriele Sansevero, Angela Chiavegato, Beatrice Vignoli, Marco Canossa, Lorena Zentilin, Nicoletta Berardi
article en
3 citations

Abstract

In the absence of explicit neuronal inputs, the glial cell astrocytes exhibit recurring intracellular Ca<sup>2+</sup> fluctuations, primarily localized at thin processes, known as Ca<sup>2+</sup> microdomains (MDs). Although spontaneous Ca<sup>2+</sup> MDs are present throughout the brain, their putative role is unknown. Here, we question whether, owing to their recurring signaling mode, spontaneous Ca<sup>2+</sup> 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 Ca<sup>2+</sup>-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 Ca<sup>2+</sup> 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.

Proceedings of the National Academy of SciencesVol. 122(42)
Istituto di Scienza e Tecnologie dell'Informazione "Alessandro Faedo" (IT), University of Padua (IT), University of Trento (IT), National Academies of Sciences, Engineering, and Medicine (US), Czech Academy of Sciences, Institute of Biophysics (CZ), National Enterprise for NanoScience and NanoTechnology (IT), Neuroscience Institute (IT), Istituto Ortopedico Rizzoli (IT), National Research Council (RO), National Research Council (IT), University of Florence (IT), International Centre for Genetic Engineering and Biotechnology (IT)
Openalex Percentile: Top 9%
Neuroinflammation and Neurodegeneration Mechanisms
2.53
DOIOpen Access PDFOpenAlex
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