Data-driven synapse classification reveals a logic of glutamate receptor composition DOI Creative Commons
Kristina D. Micheva, Anish K. Simhal,

Jenna Schardt

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

Summary The rich diversity of synapses facilitates the capacity neural circuits to transmit, process and store information. Here, we used multiplex super-resolution proteometric imaging through array tomography define features single in adult mouse neocortex. We find that glutamatergic cluster into subclasses parallel distinct biochemical functional categories receptor subunits: GluA1/4, GluA2/3 GluN1/GluN2B. Two these align with physiological expectations based on synaptic plasticity: large AMPAR-rich may represent potentiated synapses, whereas small NMDAR-rich suggest “silent” synapses. NMDA content correlates spine neck diameter, thus potential for coupling parent dendrite. Conjugate tomography’s rigorous registration immunofluorescence electron microscopy provides validation future studies other systems. No barriers prevent generalization this approach species, laying a foundation human disorders therapeutics. Highlights enables validates single-synapse proteometry Glutamate identifies places synapse ultrastructural context Subclasses established molecular plasticity Graphical Abstract

Language: Английский

Data-driven synapse classification reveals a logic of glutamate receptor composition DOI Creative Commons
Kristina D. Micheva, Anish K. Simhal,

Jenna Schardt

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

Summary The rich diversity of synapses facilitates the capacity neural circuits to transmit, process and store information. Here, we used multiplex super-resolution proteometric imaging through array tomography define features single in adult mouse neocortex. We find that glutamatergic cluster into subclasses parallel distinct biochemical functional categories receptor subunits: GluA1/4, GluA2/3 GluN1/GluN2B. Two these align with physiological expectations based on synaptic plasticity: large AMPAR-rich may represent potentiated synapses, whereas small NMDAR-rich suggest “silent” synapses. NMDA content correlates spine neck diameter, thus potential for coupling parent dendrite. Conjugate tomography’s rigorous registration immunofluorescence electron microscopy provides validation future studies other systems. No barriers prevent generalization this approach species, laying a foundation human disorders therapeutics. Highlights enables validates single-synapse proteometry Glutamate identifies places synapse ultrastructural context Subclasses established molecular plasticity Graphical Abstract

Language: Английский

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