Published on Fri Apr 16 2021

Spike-timing-dependent plasticity rewards synchrony rather than causality

Anisimova, M., van Bommel, B., Wiegert, J. S., Mikhaylova, M., Oertner, T. G., Gee, C. E.

Spike-timing-dependent plasticity (STDP) is a candidate mechanism for information storage in the brain. However, whole-cell recordings required for the experimental induction of STDP are typically limited to one hour. Here we use spectrally separated optogenetic stimulation to fire precisely timed action potentials (spikes) in CA3 and CA1 pyramidal cells. We observed timing-dependent depression and timing- dependent potentiation (tLTP) depending on the sequence of spiking.

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Abstract

Spike-timing-dependent plasticity (STDP) is a candidate mechanism for information storage in the brain, but the whole-cell recordings required for the experimental induction of STDP are typically limited to one hour. This mismatch of time scales is a long-standing weakness in synaptic theories of memory. Here we use spectrally separated optogenetic stimulation to fire precisely timed action potentials (spikes) in CA3 and CA1 pyramidal cells. Twenty minutes after optogenetic induction of STDP (oSTDP), we observed timing-dependent depression (tLTD) and timing-dependent potentiation (tLTP), depending on the sequence of spiking. As oSTDP does not require electrodes, we could also assess the strength of these paired connections three days later. At this late time point, late tLTP was observed for both causal (CA3 before CA1) and anti-causal (CA1 before CA3) timing, but not for asynchronous activity patterns ({Delta}t = 50 ms). Blocking activity after induction of oSTDP prevented stable potentiation. Our results confirm that neurons wire together if they fire together, but suggest that synaptic depression after anti-causal activation (tLTD) is a transient phenomenon. HighlightsO_LIOptogenetic induction of spike-timing-dependent plasticity at Schaffer collateral synapses C_LIO_LICausal pairing induces potentiation whereas anti-causal pairing induces depression during patch-clamp recordings. C_LIO_LIThree days after optogenetic induction, the consequence of STDP is potentiation (tLTP) irrespective of spiking order. C_LIO_LILate tLTP requires ongoing activity in the days following oSTDP. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/863365v4_ufig1.gif" ALT="Figure 1"> View larger version (19K): [email protected]@[email protected][email protected]_HPS_FORMAT_FIGEXP M_FIG C_FIG