Fig. 5. Sequences of presynaptic de- and hyperpolarizations boost recruitment of postsynaptic action potentials, resulting in lasting stabilization of synapses.
a Top: Schematic depicting multineuron patch-clamp recording of convergent synaptic motif. ‘Control’ and ‘Depol→Hyperpol’ conditions followed by trains of action potentials (AP) were induced in an alternating fashion in presynaptic neurons. Bottom: First two rows show exemplary voltage traces of presynaptic neurons. Third row depicts superimposed trials of postsynaptic traces. Fourth row shows summary histogram (n = 6 experiments; 50 ms bins). b Presynaptic AP and averaged excitatory postsynaptic potential (EPSP) of an exemplary synapse before and after ‘Pre drive post’ paradigm, which consisted of synchronous initiation of the ‘Depol→Hyperpol’ protocol in presynaptic neurons of a convergent motif to trigger postsynaptic APs, as shown in superimposed traces (sustained current was injected into postsynaptic neuron during induction; induction was typically repeated 25 times). c ‘Pre fail to drive post’ paradigm, where postsynaptic neurons were held at a more negative membrane potential, so that synapses didn’t trigger postsynaptic APs. d Mean EPSP amplitudes plotted over time for the two paradigms (normalized to pre-induction period; mean ± s.e.m). e EPSP amplitudes for time window 80–160 s after end of induction (normalized to pre-induction period; n = 9 synapses for ‘Pre drive post’, n = 8 synapses for ‘Pre fail to drive post’; two-sided Mann-Whitney U test; mean ± s.e.m). f Averaged EPSPs of two exemplary synapses before induction, as well as 5–10 and 15–20 minutes after start of induction. Paradigms consisted of 500-ms current injections to elicit associated pre- and postsynaptic trains of APs (‘Associative’) or isolated presynaptic trains of APs (‘Non-associative’). The induction was repeated 9 times over a period of 5 minutes (arrows in panel g). g Mean EPSP amplitudes plotted over time for the two paradigms (normalized to pre-induction period; mean ± s.e.m). h EPSP amplitudes for time window 15–20 minutes (normalized to pre-induction period; n = 27 synapses for ‘Associative’, n = 14 synapses for ‘Non-associative’; two-sided Mann-Whitney U test; mean ± s.e.m). i Concept of coupled vs. uncoupled sleep oscillations and their short- and long-term effect on synaptic strength. Source data are provided as a Source Data file.