A spike-timing-dependent plasticity rule for dendritic spines

Sabrina Tazerart,Soledad Miranda-Rottmann,Roberto Araya,Diana E Mitchell

doi:10.1038/s41467-020-17861-7

Sabrina Tazerart, Soledad Miranda-Rottmann + Show 2 more

Open Access

https://doi.org/10.1038/s41467-020-17861-7

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Abstract

The structural organization of excitatory inputs supporting spike-timing-dependent plasticity (STDP) remains unknown. We performed a spine STDP protocol using two-photon (2P) glutamate uncaging (pre) paired with postsynaptic spikes (post) in layer 5 pyramidal neurons from juvenile mice. Here we report that pre-post pairings that trigger timing-dependent LTP (t-LTP) produce shrinkage of the activated spine neck and increase in synaptic strength; and post-pre pairings that trigger timing-dependent LTD (t-LTD) decrease synaptic strength without affecting spine shape. Furthermore, the induction of t-LTP with 2P glutamate uncaging in clustered spines (<5 μm apart) enhances LTP through a NMDA receptor-mediated spine calcium accumulation and actin polymerization-dependent neck shrinkage, whereas t-LTD was dependent on NMDA receptors and disrupted by the activation of clustered spines but recovered when separated by >40 μm. These results indicate that synaptic cooperativity disrupts t-LTD and extends the temporal window for the induction of t-LTP, leading to STDP only encompassing LTP.

Highlights

The structural organization of excitatory inputs supporting spike-timing-dependent plasticity (STDP) remains unknown
We asked what patterns of activity and structural organization of excitatory synaptic inputs support the generation of timing-dependent long-term potentiation (LTP) (t-LTP) and timing-dependent long-term depression (LTD) (t-LTD), and which morphological, biophysical, and molecular changes observed in dendritic spines can account for the induction of t-LTP and t-LTD?
Control experiments showed no significant change in uncaging-induced excitatory postsynaptic potential (uEPSP) amplitude or spine morphology following the STDP protocol when either backpropagating AP (bAP) or synaptic stimulation were applied in isolation, or when these parameters were monitored without any STDP protocol (Supplementary Fig. 3)

Summary

Introduction

The structural organization of excitatory inputs supporting spike-timing-dependent plasticity (STDP) remains unknown. A variation of LTP and LTD has been described in pyramidal neurons that involve the pairing of pre- and postsynaptic action potentials (APs), known as spike-timing-dependent plasticity (STDP)[10,11,12,13,14]. We show that synaptic cooperativity, induced by the co-activation of only two clustered spines using 2P glutamate uncaging, disrupts t-LTD (

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