Proximity of astrocyte leaflets to the synapse determines memory strength Article Swipe
Aina Badia‐Soteras
,
Tim S. Heistek
,
Mandy S. J. Kater
,
Adrian Negrean
,
Huibert D. Mansvelder
,
Baljit S. Khakh
,
Rogier Min
,
August B. Smit
,
Mark H. G. Verheijen
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.01.30.478393
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.01.30.478393
Summary Astrocyte distal processes, known as leaflets or perisynaptic astrocyte processes (PAPs), fine-tune synaptic activity by clearing neurotransmitters and limiting extrasynaptic glutamate diffusion. While learning and memory depends on orchestrated synaptic activity of neuronal ensembles within the hippocampus, it is becoming increasingly evident that astrocytes residing in the environment of these synapses play a central role in shaping memories. However, how astroglial synaptic coverage contributes to mnemonic processing remains largely unknown. Here, we targeted astrocyte leaflet structure in vivo by depleting Ezrin, an integral leaflet-structural protein, in astrocytes of the adult hippocampal CA1 using a CRISPR-Cas9 genetic approach. This resulted in significantly smaller astrocyte territories and reduced astroglial synaptic coverage. In addition, using genetically encoded glutamate sensors and whole-cell patch-clamp recordings from pyramidal neurons, we found that Ezrin deletion and the resultant manipulation of leaflet structure boosted extrasynaptic glutamate diffusion and NMDA-receptor activation. Importantly, these cellular phenotypes translated to enhanced fear memory expression that was accompanied by increased activation of CA1 pyramidal neurons in the days after learning occurred. We show that Ezrin is critical for astrocyte morphology as well as for adult hippocampal synapse integrity and function. Our data show that astrocyte leaflet structure gates memory strength by regulating glutamate spillover in the vicinity of memory-related synaptic activity.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2022.01.30.478393
- https://www.biorxiv.org/content/biorxiv/early/2022/01/31/2022.01.30.478393.full.pdf
- OA Status
- green
- Cited By
- 3
- References
- 56
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4210630176
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4210630176Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2022.01.30.478393Digital Object Identifier
- Title
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Proximity of astrocyte leaflets to the synapse determines memory strengthWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-01-31Full publication date if available
- Authors
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Aina Badia‐Soteras, Tim S. Heistek, Mandy S. J. Kater, Adrian Negrean, Huibert D. Mansvelder, Baljit S. Khakh, Rogier Min, August B. Smit, Mark H. G. VerheijenList of authors in order
- Landing page
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https://doi.org/10.1101/2022.01.30.478393Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2022/01/31/2022.01.30.478393.full.pdfDirect link to full text PDF
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-
YesWhether a free full text is available
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-
greenOpen access status per OpenAlex
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-
https://www.biorxiv.org/content/biorxiv/early/2022/01/31/2022.01.30.478393.full.pdfDirect OA link when available
- Concepts
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Astrocyte, Neuroscience, Hippocampal formation, Glutamate receptor, AMPA receptor, Hippocampus, Synapse, Biology, Receptor, Central nervous system, BiochemistryTop concepts (fields/topics) attached by OpenAlex
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3Total citation count in OpenAlex
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2023: 1, 2022: 2Per-year citation counts (last 5 years)
- References (count)
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56Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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