Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum
- RIKEN, Japan
- Okinawa Institute of Science and Technology Graduate University, Japan
- Brain Research Institute, Niigata University, Japan
- Niigata University, Japan
Abstract
Experience-dependent plasticity is a key feature of brain synapses for which neuronal N-Methyl-D-Aspartate receptors (NMDARs) play a major role, from developmental circuit refinement to learning and memory. Astrocytes also express NMDARs although their exact function has remained controversial. Here we identify in mouse hippocampus, a circuit function for GluN2C NMDAR, a subtype highly expressed in astrocytes, in layer-specific tuning of synaptic strengths in CA1 pyramidal neurons. Interfering with astrocyte NMDAR or GluN2C NMDAR activity reduces the range of presynaptic strength distribution specifically in the stratum radiatum inputs without an appreciable change in the mean presynaptic strength. Mathematical modeling shows that narrowing of the width of presynaptic release probability distribution compromises the expression of long-term synaptic plasticity. Our findings suggest a novel feedback signaling system that uses astrocyte GluN2C NMDARs to adjust basal synaptic weight distribution of Schaffer collateral inputs, which in turn impacts computations performed by the CA1 pyramidal neuron.
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All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 3 and 4.
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Author details
Funding
Japan Society for the Promotion of Science (Overseas Research Fellow (P14760))
- Peter H Chipman
Japan Society for the Promotion of Science (Core-to-Core Program (JPJSCCA20170008))
- Yukiko Goda
MEXT Grants in Aid for Scientific Research (15H04280)
- Yukiko Goda
MEXT Grants in Aid for Scientific Research (18H05213)
- Tomoki Fukai
RIKEN Center for Brain Science
- Yukiko Goda
Uehara Memorial Foundation
- Yukiko Goda
Japan AMED Brain/MINDS
- Yukiko Goda
MEXT Grants in Aid for Scientific Research (19K16885)
- Chi Chung Alan Fung
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were approved by the RIKEN Animal Experiments Committee and performed in accordance with the RIKEN rules and guidelines. [Animal Experiment Plan Approval no. W2021-2-015(2)]
Copyright
© 2021, Chipman et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum
eLife 10:e70818.
https://doi.org/10.7554/eLife.70818
