V(t) is corrected by V(t) = Vh – Rs∗I(t), where Rs was the effective series resistance and Vh is the applied holding voltage. Membrane potential responses were derived using a single-compartment neuron model (Somers et al., 1995, Troyer et al., 1998 and Liu et al., 2010): Vm(t+dt)=−dtC[Ge(t)∗(Vm(t)−Ee)+Gi(t)∗(Vm(t)−Ei)+Gr(Vm(t)−Er)]+Vm(t)where

Vm(t) is the membrane potential at time t, C the whole-cell capacitance, Gr the resting leak conductance, Er the resting membrane potential (−60 mV). C was measured during experiments and Gr was calculated based Cobimetinib on the equation Gr = C∗Gm/Cm, where Gm, the specific membrane conductance is 1e – 5 S/cm2, and Cm, the specific membrane capacitance is 1e – 6 F/cm2. To estimate spiking responses, the spike threshold was set at 22 mV above the resting membrane potential. After each spike, membrane potential was returned to 10mV above the resting level for a refractory period of 5 ms. To quantify the strength of

orientation selectivity, the responses to drifting sinusoidal gratings or bars of two directions at each orientation were averaged to obtain the orientation tuning curve between 0 and 180 degrees, which was then fit with a Gaussian function R(θ) = A∗exp(−0.5∗(θ − φ)2/σ2) + B. φ is the preferred orientation and σ controls the tuning width. For inhibitory responses, when the tuning curve was too flat to be fitted with a Gaussian function, σ was arbitrarily set as 100°. The orientation selectivity index (OSI) is defined as (Rpref – Rorth)/(Rpref + Rorth) = A/(A + 2∗B), where Rpref is the response level at the angle of φ, and Rorth else is that at the angle of φ + 90°. A simple model was built with a neuron receiving PD0332991 both excitatory and inhibitory

synaptic inputs. Synaptic conductance was simulated as: G=Gmax∗(1−exp(−(t−t0)/τ1))∗exp(−(t−t0)/τ2),fort>t0,in which t0 is the onset time, and τ 1 = 2.8 s and τ2 = 0.17 s for both excitatory and inhibitory conductances ( Figure 4A). The onset of the inhibitory response was set at 50 ms after that of the excitatory response. Membrane potentials were derived similarly as described above from the simulated synaptic conductances. For Figure 4A, the peak conductance of excitation varied from 0.01 to 10 nS. Inhibition was as strong as, twice as strong as, or three times as strong as excitation. For Figure 4D, the tuning curves were based on average experimental data, and the maximum excitatory conductance was 1.5 nS. To derive the tuning curve for spiking responses, a threshold-and-linear transformation ( Carandini and Ferster, 2000) was used to derive peak firing rate, which was proportional to the peak depolarizing potential subtracting the spike threshold (22 mV). A power-law spike thresholding scheme ( Miller and Troyer, 2002 and Priebe and Ferster, 2008) was applied as: R(Vm)=k[Vm−Vrest]+PR is the firing rate, k is the gain factor (set as 9e5 to obtain experimentally observed firing rates), p (= 2, 3, or 5) is the exponent.