An astrocytic AMPAR-dependent parity signal preserves synaptic strength
- 1Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Aligning Science Across
Abstract
Astrocytic processes closely associate with excitatory synapses and express AMPARs, positioning them to sense the same glutamate signals as neurons. Whether a mismatch between neuronal and astrocytic glutamate sensing affects synaptic physiology is unknown. Using AstroHTP, an extension of Drug Acutely Restricted by Tethering (DART) for cell-type-specific pharmacology, we found that acute astrocytic AMPAR inhibition spared neuronal AMPARs and basal transmission yet converted ongoing glutamatergic activity into a remarkably potent form of long-term depression (LTD) in mouse striatal projection neurons (SPNs). Unlike canonical presynaptic LTD, this form of LTD manifests postsynaptically, requires non-ionotropic NMDA receptor signaling, and arises when glutamate transmission occurs without a matching astrocytic signal. Astrocytic glutamate sensing through AMPARs, therefore, acts as a parity signal that verifies transmission and stabilizes active synapses.
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BibTeX
@misc{elazar2026astrocytic,
title = {{An astrocytic AMPAR-dependent parity signal preserves synaptic strength}},
author = {N. Elazar and J. R. Ravenel and J. Kim and T. Vaidyanathan and O. Wirfel-Farenchak and K. Uryu and S. S. X. Lim and J. R. Roach and W. Zhang and X. Cao and M. E. van Praag and H. Yan and G. Yu and M. R. Tadross and C. Eroglu},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.08.757679},
url = {https://www.biorxiv.org/content/10.64898/2026.10.08.757679v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - An astrocytic AMPAR-dependent parity signal preserves synaptic strength
AU - N. Elazar
AU - J. R. Ravenel
AU - J. Kim
AU - T. Vaidyanathan
AU - O. Wirfel-Farenchak
AU - K. Uryu
AU - S. S. X. Lim
AU - J. R. Roach
AU - W. Zhang
AU - X. Cao
AU - M. E. van Praag
AU - H. Yan
AU - G. Yu
AU - M. R. Tadross
AU - C. Eroglu
PY - 2026
DA - 2026/10/08
PB - bioRxiv
DO - 10.64898/2026.10.08.757679
UR - https://www.biorxiv.org/content/10.64898/2026.10.08.757679v1
AB - Astrocytic processes closely associate with excitatory synapses and express AMPARs, positioning them to sense the same glutamate signals as neurons. Whether a mismatch between neuronal and astrocytic glutamate sensing affects synaptic physiology is unknown. Using AstroHTP, an extension of Drug Acutely Restricted by Tethering (DART) for cell-type-specific pharmacology, we found that acute astrocytic AMPAR inhibition spared neuronal AMPARs and basal transmission yet converted ongoing glutamatergic activity into a remarkably potent form of long-term depression (LTD) in mouse striatal projection neurons (SPNs). Unlike canonical presynaptic LTD, this form of LTD manifests postsynaptically, requires non-ionotropic NMDA receptor signaling, and arises when glutamate transmission occurs without a matching astrocytic signal. Astrocytic glutamate sensing through AMPARs, therefore, acts as a parity signal that verifies transmission and stabilizes active synapses.
ER -