Unifying Long-Term Plasticity Rules for Excitatory Synapses by Modeling Dendrites of Cortical Pyramidal Neurons

Christian Ebner,Claudia Clopath,Peter Jedlicka,Hermann Cuntz

doi:10.1016/j.celrep.2019.11.068

Abstract

SummaryA large number of experiments have indicated that precise spike times, firing rates, and synapse locations crucially determine the dynamics of long-term plasticity induction in excitatory synapses. However, it remains unknown how plasticity mechanisms of synapses distributed along dendritic trees cooperate to produce the wide spectrum of outcomes for various plasticity protocols. Here, we propose a four-pathway plasticity framework that is well grounded in experimental evidence and apply it to a biophysically realistic cortical pyramidal neuron model. We show in computer simulations that several seemingly contradictory experimental landmark studies are consistent with one unifying set of mechanisms when considering the effects of signal propagation in dendritic trees with respect to synapse location. Our model identifies specific spatiotemporal contributions of dendritic and axo-somatic spikes as well as of subthreshold activation of synaptic clusters, providing a unified parsimonious explanation not only for rate and timing dependence but also for location dependence of synaptic changes.

Highlights

Adaptive behavior, guided by learning and memory processes, can be seen as a macroscopic manifestation of microscopic long-term changes in synaptic strength (Bliss and Collingridge, 1993)
The location of synapses along the dendritic tree was shown to play an important role, with long-term depression (LTD) often becoming more prominent in distal synapses (Froemke et al, 2005; Sjostrom and Hausser, 2006), a likely consequence of voltage attenuation of backpropagating action potentials in dendrites (Stuart et al, 1997), where long-term potentiation (LTP) was recovered by boosting bAPs through dendritic current injection or cooperative synaptic inputs (Sjostrom and Hausser, 2006)
Phospholipase C (PLC) integrates these two signals in the process of synthesizing endocannabinoids (Hashimotodani et al, 2005), which retrogradely act on presynaptic type 1 cannabinoid receptors (CB1Rs) to reduce transmitter release probability (Heifets and Castillo, 2009), causing presynaptically expressed LTD (pre-LTD)

Summary

Introduction

Adaptive behavior, guided by learning and memory processes, can be seen as a macroscopic manifestation of microscopic long-term changes in synaptic strength (Bliss and Collingridge, 1993). The location of synapses along the dendritic tree was shown to play an important role, with LTD often becoming more prominent in distal synapses (Froemke et al, 2005; Sjostrom and Hausser, 2006), a likely consequence of voltage attenuation of backpropagating action potentials (bAPs) in dendrites (Stuart et al, 1997), where LTP was recovered by boosting bAPs through dendritic current injection or cooperative synaptic inputs (Sjostrom and Hausser, 2006) In addition to these effects of frequency and location on STDP, plasticity can be induced by depolarization that originates from other sources besides bAPs in the postsynaptic neuron, e.g., dendritic Ca2+ spikes (Golding et al, 2002; Kampa et al, 2006; Letzkus et al, 2006), N-methyl-D-aspartate (NMDA) spikes (Brandalise et al, 2016; Gordon et al, 2006), or excitatory postsynaptic potentials (EPSPs) alone (Sandler et al, 2016; Weber et al, 2016).

Methods

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Discussion

Conclusion