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bioRxiv · 10.64898/2026.10.08.757679

An astrocytic AMPAR-dependent parity signal preserves synaptic strength

Elazar, N.·Ravenel, J. R.·Kim, J.·Vaidyanathan, T.·Wirfel-Farenchak, O.·Uryu, K.·Lim, S. S. X.·Roach, J. R.·Zhang, W.·Cao, X.·van Praag, M. E.·Yan, H.·Yu, G.·Tadross, M. R.·Eroglu, C.
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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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Elazar, N., Ravenel, J. R., Kim, J., Vaidyanathan, T., Wirfel-Farenchak, O., Uryu, K., Lim, S. S. X., Roach, J. R., Zhang, W., Cao, X., van Praag, M. E., Yan, H., Yu, G., Tadross, M. R., Eroglu, C.. 2026-10-11. An astrocytic AMPAR-dependent parity signal preserves synaptic strength. https://doi.org/10.64898/2026.10.08.757679

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