Uncovering circuit mechanisms of current sinks and sources with biophysical simulations of primary visual cortex

Abstract

Local field potential (LFP) recordings reflect the dynamics of the current source density (CSD) in brain tissue. The synaptic, cellular and circuit contributions to current sinks and sources are ill-understood. We investigated these in mouse primary visual cortex using public Neuropixels recordings and a detailed circuit model based on simulating the Hodgkin-Huxley dynamics of numerous cortical neurons belonging to 17 cell types. The model simultaneously captured spiking and CSD responses and demonstrated a two-way dissociation: Firing rates are altered with minor effects on the CSD pattern by adjusting synaptic weights, and CSD is altered with minor effects on firing rates by adjusting synaptic placement on the dendrites. We describe how thalamocortical inputs and recurrent connections sculpt specific sinks and sources early in the visual response, whereas cortical feedback crucially alters them in later stages. Our findings show that CSD analysis provides powerful constraints for modeling beyond those from considering spikes.

Uncovering population contributions to the extracellular potential in the mouse visual system using Laminar Population Analysis

“…These opposite effects will not be captured by the estimated contribution from a population where the temporal profile reflects spikes from both excitatory and inhibitory cells. In the model, the majority of the MUA was generated by excitatory cells and the primary sinks and sources was previously shown to reflect excitatory input [52]. Therefore, the error from this simplification is expected to be minor for the model.…”

“…We utilized data from simulations on the final model presented in [52], and the output data and the files and code necessary to simulate this model version are provided in the Materials and Methods section of that paper. The model was built and the simulations carried out with the Brain Modeling Tool Kit (BMTK) software [75].…”

“…Unfortunately, constructing models that can simulate extracellular potentials can be a resource intensive endeavour, both with respect to human as well as computational resources. This is especially true for large-scale network modeling required to simulate the population LFP recorded in vivo [52]. It would therefore be highly advantageous to have analysis tools that allow for uncovering of biophysical processes from experimental data without requiring the construction of a model.…”

EEG Interchannel Causality to Identify Source/Sink Phase Connectivity Patterns in Developmental Dyslexia

“…While this concept of sources/sinks is not new, it has been subject to a variety of different approaches. For example, Rimehaug et al 30 integrated it into their model of the visual cortex's local field potential, while Sotero et al 31 used it to explain the laminar distribution of phaseamplitude coupling of spontaneous current sources and sinks in rat brains. However, neither of those studies based their modeling of sources and sinks on causality relationships, instead using the electrical activity in the cerebral cortex.…”

Simulations of cortical networks using spatially extended conductance‐based neuronal models

“…A multipurpose model with a detailed spatial arrangement of neurons is suitable for such an application. Utilizing the Billeh et al (2020) model of mouse V1, Rimehaug et al (2022) were able to carry out systematic, quantitative comparisons of both LFP and spiking activity with in vivo experiments. The results revealed a substantial dissociation between circuit mechanisms underlying LFP versus spiking activity and emphasized the role of layer-and cell type-specific thalamocortical projections for generating the early LFP response and feedback projections to V1 from higher visual cortical areas in generating the later LFP response.…”