Mapping AMPA and NMDA receptors at mouse brain hippocampal synapses by cryo-ET
- 1Oregon Health & Science University | Howard Hughes Medical Institute
Abstract
AMPA and NMDA receptors are fundamental to synaptic transmission through the detection of released neurotransmitter. These ion channels open in response to glutamate binding, resulting in depolarization of the postsynaptic membrane and influx of calcium. Receptor localization plays a key role in synaptic strength, and changes in receptor number and location underpin synaptic plasticity, learning and memory. Here we apply receptor subunit-specific antibody fragments and multiplexed gold nanoparticle conjugates, together with cryo-electron tomography (cryo-ET), to elucidate the in-situ molecular organization of AMPA and NMDA receptors at hippocampal synapses in adult mouse brain tissue. AMPA receptors are predominantly found in densely packed liquid-like clusters, with interspersed NMDA receptors and adjacent NMDA receptor clusters. By direct localization of individual receptors, we provide molecular-resolution insight into the distribution of AMPA and NMDA receptors across the synapse, at peri and extrasynaptic sites, and within endocytosed vesicles. Visualization of multiple presynaptic vesicle fusion events suggests that receptors are near, but not always directly adjacent to, transmitter release sites. By mapping AMPA and NMDA receptors, and glutamate release sites, we provide receptor-resolution insight into the structure and function of brain hippocampal synapses.
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BibTeX
@misc{spangler2026mapping,
title = {{Mapping AMPA and NMDA receptors at mouse brain hippocampal synapses by cryo-ET}},
author = {C. J. Spangler and A. Matsui and H. Kim and E. V. Shiltseva and G. Dhandapani and D. J. Weingarten and R. Arnold and Y. Sugiyama and S. Jackman and J. Elferich and E. Gouaux},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.02.763697},
url = {https://www.biorxiv.org/content/10.64898/2026.11.02.763697v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Mapping AMPA and NMDA receptors at mouse brain hippocampal synapses by cryo-ET
AU - C. J. Spangler
AU - A. Matsui
AU - H. Kim
AU - E. V. Shiltseva
AU - G. Dhandapani
AU - D. J. Weingarten
AU - R. Arnold
AU - Y. Sugiyama
AU - S. Jackman
AU - J. Elferich
AU - E. Gouaux
PY - 2026
DA - 2026/11/02
PB - bioRxiv
DO - 10.64898/2026.11.02.763697
UR - https://www.biorxiv.org/content/10.64898/2026.11.02.763697v1
AB - AMPA and NMDA receptors are fundamental to synaptic transmission through the detection of released neurotransmitter. These ion channels open in response to glutamate binding, resulting in depolarization of the postsynaptic membrane and influx of calcium. Receptor localization plays a key role in synaptic strength, and changes in receptor number and location underpin synaptic plasticity, learning and memory. Here we apply receptor subunit-specific antibody fragments and multiplexed gold nanoparticle conjugates, together with cryo-electron tomography (cryo-ET), to elucidate the in-situ molecular organization of AMPA and NMDA receptors at hippocampal synapses in adult mouse brain tissue. AMPA receptors are predominantly found in densely packed liquid-like clusters, with interspersed NMDA receptors and adjacent NMDA receptor clusters. By direct localization of individual receptors, we provide molecular-resolution insight into the distribution of AMPA and NMDA receptors across the synapse, at peri and extrasynaptic sites, and within endocytosed vesicles. Visualization of multiple presynaptic vesicle fusion events suggests that receptors are near, but not always directly adjacent to, transmitter release sites. By mapping AMPA and NMDA receptors, and glutamate release sites, we provide receptor-resolution insight into the structure and function of brain hippocampal synapses.
ER -