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Jun 21, 2021

In Silico Voltage-Sensitive Dye Imaging Reveals the Emergent Dynamics of Cortical Populations

Taylor H. Newton, Michael W. Reimann, Marwan Abdellah, Grigori Chevtchenko, Eilif B. Muller, and Henry Markram , Nature Communications 2021, Volume 12, 3630, online 15 June 2021; doi: https://doi.org/10.1038/s41467-021-23901-7

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.

The scientific and technical impact of the study can be summarized as:

  • Computational modeling makes it possible to study how network-level brain phenomena emerge from many interactions among individual neurons
  • Simulations show that VSDI captures the ongoing dynamics of deep cortical layers as a result of arborizations in layer 2/3
  • In silico VSDI performed on a digital rodent neocortical slice exhibits biologically plausible spatiotemporal dynamics
  • An improved understanding of brain imaging modalities such as VSDI will augment our understanding of disease states and help to inform therapeutic interventions