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Justus
New paper out in PNAS today. Long-running collaboration between Malinow and labs brought to fruition by Kim Dore! Check it out. SYNPLA, a method to identify synapses displaying plasticity after learning
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...
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Justus 25. sij
Odgovor korisniku/ci @TonyZador
So, what is this paper about? SYNPLA is a method to label synapses in a specific pathway that recently underwent LTP. The principle is simple. We exploit the fact that after LTP GluA1 temporarily moves into the synapse from extra-synaptic pools.
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Justus 25. sij
Odgovor korisniku/ci @JustusKebschull
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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Justus 25. sij
Odgovor korisniku/ci @JustusKebschull
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.
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Justus 25. sij
Odgovor korisniku/ci @JustusKebschull
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!
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Justus 25. sij
Odgovor korisniku/ci @JustusKebschull
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.
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Justus 25. sij
Odgovor korisniku/ci @JustusKebschull
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.
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Justus 25. sij
Odgovor korisniku/ci @JustusKebschull
Intriguingly, the connection to lateral habenula is potentiated both when tone and footshock are paired or unpaired.
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Petr Znamenskiy 24. sij
That's synply fantastic!
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Arkarup Banerjee 24. sij
Odgovor korisniku/ci @JustusKebschull @TonyZador
Congrats on your first (?) last author publication!
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Justin Botterill 25. sij
Odgovor korisniku/ci @JustusKebschull @TonyZador
Congrats Justus!
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