Fig. 4: Biophysically realistic simulation of the response to cortical electrical stimulation recapitulates the in vivo results and provides potential explanatory mechanisms underlying the stereotyped evoked activity.
From: Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans
A Structure of the biophysically realistic model, modified from Krishnan et al.46. B Top: Schematic representation of cortical electrical stimulation applied to the centered half of cortical neurons (both PY and IN, highlighted). Bottom: cortical inputs to TC-neurons as function of their relative position in the network. C Representative stimulation-evoked intracellular voltage for one PY-neuron (top) and one TC-neuron (bottom). D Intracellular voltage for one representative trial for all PY (top) and TC (bottom) neurons. E Median latency of the firs- evoked-spike in the early (0–50 ms, top) and in the rebound response (75–250 ms, bottom) for PY and TC neurons (30 sessions; early responses: PY:3.15 ± 3.22 ms; TC:8.38 ± 7.03 ms; two-tailed Wilcoxon-rank-sum test, p = 1.56e-20. Rebound responses: PY:151.56 ± 11.83 ms; TC:141.80 ± 9.68 ms; two-tailed Wilcoxon-rank-sum test, p = 1.11e-04). All boxplots show median (line), 25–75 percentile (box), maximum/minimum or 1.5 interquartile range from the 25–75 percentile (whiskers). F Median intracellular voltage during baseline and during 25–100 ms response window for PY-neurons (top) and TC-neurons (bottom). The intracellular voltage of PY-neurons is not affected in the response window compared to baseline (32 rest and 32 active trials; Baseline:-63.08 ± 0.32 mV; Response:-63.16 ± 0.88 mV; Wilcoxon-rank-sum test, p = 0.46), while TC-neurons show a significant decrease of 6.26 mV (30 sessions; Baseline:-61.38 ± 0.36 mV; Response:-67.64 ± 3.13 mV; two-tailed Wilcoxon-rank-sum test, p = 3.87e-20). G Intrinsic current dynamics for one representative TC-neuron over time from the stimulation onset (0 ms). Left to right: total synaptic inputs, h-current, and T-current. H Simulated responses evoked by cortical stimulation in absence of either TRN or cortical GABAergic neurons. Top: schematic representation of the simulation when TRN neurons were silenced and the associated intracellular voltage for one representative trial for cortical (left) and thalamic (right) neurons. Bottom: schematic representation of the simulation when GABAergic cortical neurons were silenced and the associated intracellular voltage for one representative trial for PY (left) and TC (right) neurons. I Average intracellular voltage during the stimulus-induced off-period (25–100 ms) in 50-centrally-located TC-neurons across different GABA-A connectivity strength in IN- > PY (x-axis) and TRN- > TC (y-axis) connections. Source data are provided as a Source Data file.
