A calcium-based plasticity model for predicting long-term potentiation and depression in the neocortex

Abstract

Pyramidal cells (PCs) form the backbone of the layered structure of the neocortex, and plasticity of their synapses is thought to underlie learning in the brain. However, such long-term synaptic changes have been experimentally characterized between only a few types of PCs, posing a significant barrier for studying neocortical learning mechanisms. Here we introduce a model of synaptic plasticity based on data-constrained postsynaptic calcium dynamics, and show in a neocortical microcircuit model that a single parameter set is sufficient to unify the available experimental findings on long-term potentiation (LTP) and long-term depression (LTD) of PC connections. In particular, we find that the diverse plasticity outcomes across the different PC types can be explained by cell-type-specific synaptic physiology, cell morphology and innervation patterns, without requiring type-specific plasticity. Generalizing the model to in vivo extracellular calcium concentrations, we predict qualitatively different plasticity dynamics from those observed in vitro. This work provides a first comprehensive null model for LTP/LTD between neocortical PC types in vivo, and an open framework for further developing models of cortical synaptic plasticity.

Asymmetric voltage attenuation in dendrites can enable hierarchical heterosynaptic plasticity

“…CC-BY 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is * Rm divided by 2 and Cm multiplied by 2 to compensate for surface area of unmodeled spines while maintaining the membrane time constant For synapses, we used the Blue Brain Project's synapse model with NMDA receptors, VGCCs, and calcium-based long-term plasticity model [41]; details of the synaptic and calcium dynamics can be found there. The calcium-based plasticity model itself is based on [48].…”

“…As in the Hay model, effective dendritic membrane resistivity dendritic 𝑅 𝑚 is divided by two to compensate for the surface area of (unmodeled) spines and dendritic membrane capacitance dendritic 𝐶 𝑚 was doubled to ensure that the membrane time constant 𝜏 does not change. * Rm divided by 2 and Cm multiplied by 2 to compensate for surface area of unmodeled spines while maintaining the membrane time constant For synapses, we used the Blue Brain Project's synapse model with NMDA receptors, VGCCs, and calcium-based long-term plasticity model [41]; details of the synaptic and calcium dynamics can be found there. The calcium-based plasticity model itself is based on [48].…”

“…The authors would like to thank András Ecker and Giuseppe Chindemi for the use of their plastic synapse model [41], their support and helpful discussions in dealing with technical and conceptual issues over the course of this project, and for their helpful comments our manuscript. We also thank Yuri Rodrigues and Thomas Chater for their thorough comments on the manuscript.…”

“…At the active site, both NMDA and VGCCs brought substantial amounts of calcium current into the cell, allowing the calcium accumulator (i.e. the effective calcium used for plasticity in the plastic synapse model of [41] to surpass 𝜃 𝑃 , generating homosynaptic potentiation. At spines distal to the input site (i.e.…”

“…Recently, a model synapse was developed as part of the Blue Brain Project [41] which incorporates NMDA receptors, VGCCs, and calcium-dependent long-term plasticity dynamics. This synapse model (with some modifications described in Methods) enables us to explore Lisman's hypothesis about the calcium basis of heterosynaptic plasticity in a cable model of a dendrite, which can provide insight into the spatial properties of heterosynaptic plasticity.…”