New paper out in PNAS today. Long-running collaboration between Malinow and @TonyZador labs brought to fruition by Kim Dore! Check it out.
SYNPLA, a method to identify synapses displaying plasticity after learninghttps://www.pnas.org/content/early/2020/01/22/1919911117 …
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Synaptic GluA1, therefore, is a marker for recently potentiated synapses. The trick is to detect this synaptic GluA1 only in genetically or anatomically specified pathways.
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We do this by PLA. PLA is essentially a double antibody stain that results in a 1000x amplified signal only if the two proteins probed for are closer than 40nm to each other. This happens across the synaptic cleft.pic.twitter.com/BMFl674TVS
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In SYNPLA we probe for endogenous GluA1 and the pathway-specifically expressed pre-synaptic myc-NRXN. We only get a SYNPLA signal if a synapse contains both GluA1 and myc-NRXN . Extra-synaptic GluA1 is too far away from the presynaptic partner to make a signal!pic.twitter.com/lipwzUVRvl
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In the paper, we show that SYNPLA works in cultured neurons and hippocampal slice cultures. There we detect a much larger number of SYNPLA signals after chemically induced LTP than in control conditions or when LTP is blocked.pic.twitter.com/XxxhnijE2B
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Similarly, SYNPLA works on ex vivo slices of defense conditioned animals. When expressing myc-NRXN in auditory cortex and/or medial geniculate nucleus, we show that paired tone and footshock potentiate the connection to the lateral amygdala relative to controls.pic.twitter.com/3zHp4X1NZx
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Intriguingly, the connection to lateral habenula is potentiated both when tone and footshock are paired or unpaired.pic.twitter.com/BktT2SdOB1
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