Extended Data Fig. 16: Computational modeling: increased intrinsic excitability and CP-AMPAR inward rectification decreases selectivity.

a, PV-Cre;lsl-eGFP-GluA2 mice show intrinsic excitability increase in the form of a shift of the FI curve to lower input currents (Extended Data Fig. 10o). Dashed line: FI curve of PV-Cre;lsl-eGFP mice, shifted by E = 106.03 pA (fit to data). b, Model of increased intrinsic excitability: a shift of the PV cell’s FI-curve. c, Increased excitability causes a uniform increase in stimulus responses, decreasing stimulus selectivity (OSI: 0.44 vs OSI: 0.3). d, Orientation selectivity decreases for any increase in excitability. The decrease is even more pronounced in the presence of downscaled weights, mimicking a potentially decreased weight scale (black line; cf. Extended Data Fig. 10f). Magenta and green dots indicate examples shown in (b), (c). e, A range of increases in excitability, each compensated by a homeostatic synaptic scaling to preserve the mean rate (inset). f, Tuning curves for different levels of increased excitability. g, As (f), but normalized to the maximum response. h, Orientation selectivity monotonically decreases with increasing excitability, even for commensurately decreasing synaptic scaling. i-n, Alternative models of inward rectification. i, Average I-V relationship in calcium permeable (CP) and calcium-impermeable (CI) receptors, measured in excitatory neurons of wild-type and GluA2 knockout mice, respectively, derived from Lu et al.⁹⁶ j, Conductance measured from k, estimated as current / voltage. k, Model of voltage or rate-dependent desensitization of inputs, parametrized by the relative portion α of CP versus CI conductances. The conductance in PV-Cre;lsl-eGFP-GluA2 neurons was modeled as CI-AMPARs only (green, CP-AMPAR coefficient λ = 0). The conductance in PV-Cre;lsl-eGFP neurons was modeled as a combination of CI and CP receptors (magenta, CP-AMPAR coefficient λ = 0.8). l, Increased responses to preferred stimuli in simulated PV-Cre;lsl-eGFP-GluA2 neurons. Orientation selectivity index (OSI): 0.49 (eGFP) and 0.55 (GluA2). m, As (d), but normalized by maximum response. n, Orientation selectivity monotonically decreases as the portion of CP-AMPARs λ increases. Dots indicate values used in panels k, l, m.