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What resolves this contention: Interpretation of paradoxical-effect experiments as a diagnostic of recurrent E→E coupling: Sanzeni 2020 uses wide-field VGAT activation (perturbing all inhibitory cells) to demonstrate ISN regime, but the same authors' 2020 theory paper shows that in realistic multi-interneuron networks the paradoxical effect alone does not uniquely identify an ISN. / Mouse V1, S1, and motor cortex operate as ISNs during spontaneous activity, with strong recurrent E→E gain demonstrated by paradoxical responses to widespread VGAT-ChR2 optogenetic inhibition. / In four-population networks including PYR/PV/SST/VIP, the paradoxical effect to PV perturbation can occur even when the network is NOT in the ISN regime — so paradoxical response is not a unique signature of strong recurrent E→E gain.
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May 16, 2026
Updated
May 17, 2026

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