Granger Causality analysis correctly identifies the inhibitory relationship between model neurons. (A) Three quadratic integrate-and-fire Izhikevitch neurons  were coupled in a cyclically inhibitory fashion (network topology schematic in panel C) and made to fire slowly and with variability (rate = 2.5 Hz with CV = 0.6, black, dark gray, light gray traces correspond to individual model cells). (B) Traces show an average spike (top panel) and average voltage waveforms in each cell in a 60 ms time window triggered on a spike occurring in the presynaptic neuron (bottom three panels). Trace gray scales correspond to the legend in A. (C) Network layout includes three cells that inhibit each other in a cyclical fashion. Synaptic maximal conductances are all uniformly set to 0.1 nS. Filled circles indicate inhibition. Gray scales of cells (numbered 1, 2, 3) correspond to the legend in A. (D) Granger causality analysis predicts a causal relationship closely matching synaptic architecture. Filled triangles indicate the directionality of the statistically significant Granger causal relationships between cells. Granger values and P-values are indicated in the figure. (E) Pyloric-like network topology comparable to that shown in Figure 1B. Synaptic coupling between cells 1 and 2 is reciprocal as is the synaptic coupling between cell 2 and cell 3. Cell 1 additionally inhibits cell 3 but cell 3 does not synapse onto cell 1. (F) Granger causality analysis succeeded in reconstructing this network architecture. Statistically significant Granger values were found for all synaptic connections between cells 1 and 2 as well as for cells 2 and 3. For the synapse from cell 1 to cell 3 the Granger value came close to the threshold for statistical significance (line drawn as dashed to indicate lack of significance). The Granger value for the non-existent synapse from cell 3 to cell 1 (not drawn) was non-significant (P = 0.33).