Asymmetric voltage attenuation in dendrites can enable hierarchical heterosynaptic plasticity

Abstract

Long-term synaptic plasticity has been shown to be mediated via calcium concentration ([Ca2+]). Using a synaptic model which implements calcium-based long-term plasticity via two sources of Ca2+, NMDA receptors and voltage-gated calcium channels (VGCCs), we show in dendritic cable simulations that the interplay between these two calcium sources can result in a diverse array of heterosynaptic effects. When spatially clustered synaptic input produces an NMDA spike, the resulting dendritic depolarization can activate VGCCs at other spines, resulting in heterosynaptic plasticity. Importantly, NMDA spike activation at a given dendritic location will tend to depolarize dendritic regions that are located distally to the input site more than dendritic sites that are proximal to it. This dendritic asymmetry results in a hierarchical heterosynaptic plasticity effect in branching dendrites, where clustered inputs to a proximal branch induce heterosynaptic plasticity primarily at branches that are distal to it. We also explore how simultaneously activated synaptic clusters located at different dendritic locations synergistically affect each other as well as the heterosynaptic plasticity of an inactive synapse "sandwiched" between them. We conclude that dendrites enable a sophisticated form of plastic supervision wherein NMDA spike induction can be spatially targeted to produce plasticity at specific dendritic regions.

Ca2+-dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses

“…To provide more detail than the heat map of dendritic depolarization (Figure 6A), a plot of peak membrane potential as a function of distance from the soma was generated; it shows the strong attenuation with distance from the dendritic spike activation site (Figure 6C). However, in agreement with previous work, 66,69 distal to the site of spike generation, the peak membrane potential did not fall off significantly with distance (Figure 6C). To link this voltage measurement to the opening of CaV1.3 Ca 2+ channels (and PDE1 activation), both a dendritic heat map and a detailed distance plot of CaV1.3 channel conductance was constructed (Figures 6D-6F).…”

The Calcitron: A Simple Neuron Model That Implements Many Learning Rules via the Calcium Control Hypothesis

“…Another important feature of biological neurons not incorporated into the calcitron is the spatial distribution of synapses on a neuron’s dendrites. This is especially relevant for heterosynaptic plasticity, which depends on the location of synapses relative to each other as well as their absolute location on the dendritic tree (Chater & Goda, 2021; Chistiakova et al, 2014; Moldwin et al, 2022; Tong et al, 2021). The calcitron can be augmented to include location-dependent heterosynaptic plasticity on a single dendrite following the schemes of the clusteron (Mel, 1991) or the G-clusteron (Moldwin et al, 2021) or to explicitly include a branching dendrite to account for the branch-dependent hierarchical heterosynaptic plasticity effect we posited in previous work (Moldwin et al, 2022).…”

“…This is especially relevant for heterosynaptic plasticity, which depends on the location of synapses relative to each other as well as their absolute location on the dendritic tree (Chater & Goda, 2021; Chistiakova et al, 2014; Moldwin et al, 2022; Tong et al, 2021). The calcitron can be augmented to include location-dependent heterosynaptic plasticity on a single dendrite following the schemes of the clusteron (Mel, 1991) or the G-clusteron (Moldwin et al, 2021) or to explicitly include a branching dendrite to account for the branch-dependent hierarchical heterosynaptic plasticity effect we posited in previous work (Moldwin et al, 2022). The spatial structure of the dendrite can also influence homeostatic plasticity (Rabinowitch & Segev, 2006a, 2006b) as well as how inhibitory inputs affect plasticity at excitatory synapses (Bar-Ilan et al, 2012).…”

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“…) or experiments (Debanne et al, 1998;Inglebert et al, 2020;Kampa et al, 2006;Tazerart et al, 2020) (For a recent review see (Debanne & Inglebert, 2023)). Consequently, there is increasing interest in the role of calcium across multiple nearby synapses on sections of neurite and associated heterosynaptic plastic events resulting from stimulation, plasticity induction at a dendritic site and how this alters the synaptic weight or the threshold for plastic change in unactivated nearby synapses (Abraham & Goddard, 1983;Chistiakova & Volgushev, 2009;Chistiakova et al, 2014;Harvey & Svoboda, 2007;Kourosh-Arami et al, 2023;Moldwin et al, 2023;Pozo & Goda, 2010). This is, however, one side of the coin of an overarching theme we have called Heterosynaptic interactions due to the bidirectional nature of voltage and calcium signalling in dendrites.…”

“…One topic that has gained increasing attention is the role and induction of heterosynaptic plasticity within dendrites, where the induction of synaptic plasticity caused by pre-synaptic and post-synaptic activity at one position causes plasticity changes at different nearby locations Chistiakova & Volgushev, 2009;Moldwin et al, 2023;Pozo & Goda, 2010;Tong et al, 2021). This points to the question that deserves further investigation of the role that the spatial spread of internal calcium has on the plasticity of synapses and specifically, the interplay between neuronal morphology on the spread of activity within dendrites and how this affects calcium concentration and the expression of synaptic plasticity.…”