In silico voltage-sensitive dye imaging reveals the emergent dynamics of cortical populations

Taylor H Newton,Michael W Reimann,Marwan Abdellah,Henry Markram,Eilif B Muller,Grigori Chevtchenko

doi:10.1038/s41467-021-23901-7

Abstract

Voltage-sensitive dye imaging (VSDI) is a powerful technique for interrogating membrane potential dynamics in assemblies of cortical neurons, but with effective resolution limits that confound interpretation. To address this limitation, we developed an in silico model of VSDI in a biologically faithful digital reconstruction of rodent neocortical microcircuitry. Using this model, we extend previous experimental observations regarding the cellular origins of VSDI, finding that the signal is driven primarily by neurons in layers 2/3 and 5, and that VSDI measurements do not capture individual spikes. Furthermore, we test the capacity of VSD image sequences to discriminate between afferent thalamic inputs at various spatial locations to estimate a lower bound on the functional resolution of VSDI. Our approach underscores the power of a bottom-up computational approach for relating scales of cortical processing.

Highlights

Voltage-sensitive dye imaging (VSDI) is a powerful technique for interrogating membrane potential dynamics in assemblies of cortical neurons, but with effective resolution limits that confound interpretation
To quantify the similarity between the evoked response dynamics of our model and those reported in literature, we conducted a series of whisker flick-like trials and examined the spread of activity
Our stimulation protocol consisted of a single pulse of activity in 60 contiguous thalamocortical (TC) fibers emanating from a virtual ventral posteromedial nucleus (VPM) projecting to the geometric center of a concentric arrangement of seven neocortical microcircuitry (NMC)

Summary

Introduction

Voltage-sensitive dye imaging (VSDI) is a powerful technique for interrogating membrane potential dynamics in assemblies of cortical neurons, but with effective resolution limits that confound interpretation. To address this limitation, we developed an in silico model of VSDI in a biologically faithful digital reconstruction of rodent neocortical microcircuitry. Intrinsic optical imaging is limited by a slow time constant (on the order of seconds10,11), rendering it ill-suited for capturing temporal changes in ongoing activity To this end, VSDI has added a dynamic component to the understanding of neural assemblies. We corrected the compartment voltages to account for the effects of dye penetration and light transport in cortical tissue (Fig. 1d), and collected this data into voxels (Fig. 1d, e)

Methods

Results

Conclusion