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SYNPLA, a method to identify synapses displaying plasticity after learning
Contributed by Roberto Malinow, December 19, 2019 (sent for review November 13, 2019; reviewed by Joseph E. LeDoux and Mats Nilsson)

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Significance
When an animal forms a memory, synapses in specific brain pathways change their strength. Pinpointing which synapses and pathways are modulated in any given learning paradigm, however, is technically challenging and needs to be performed one candidate connection at a time. Here we present SYNPLA, a tool to quickly detect strengthened synapses in genetically or anatomically defined pathways across the brain. To do so, we exploit the temporary translocation of AMPA receptor GluA1 into newly strengthened synapses. Using an assay that can identify proteins less than 40 nm away, we label only synapses that contain both GluA1 and a presynaptic protein exogenously expressed in a specific pathway. SYNPLA thus provides a pathway- and synapse-specific screening tool for memory formation.
Abstract
Which neural circuits undergo synaptic changes when an animal learns? Although it is widely accepted that changes in synaptic strength underlie many forms of learning and memory, it remains challenging to connect changes in synaptic strength at specific neural pathways to specific behaviors and memories. Here we introduce SYNPLA (synaptic proximity ligation assay), a synapse-specific, high-throughput, and potentially brain-wide method capable of detecting circuit-specific learning-induced synaptic plasticity.
Footnotes
- ↵1To whom correspondence may be addressed. Email: rmalinow{at}ucsd.edu or justus{at}kebschull.me.
Author contributions: K.D., A.M.Z., R.M., and J.M.K. designed research; K.D., Y.P., S.A., H.Z., S.G., S.M., and J.M.K. performed research; K.D., Y.P., J.S.L., R.M., and J.M.K. analyzed data; and K.D., A.M.Z., R.M., and J.M.K. wrote the paper.
Reviewers: J.E.L., New York University; and M.N., Stockholm University.
The authors declare no competing interest.
This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1919911117/-/DCSupplemental.
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