In normalization models, a large pool of cortical interneurons of all different preferred orientations generates shunting inhibition proportional in strength to stimulus contrast at all orientations (Carandini et al., 1997, DeAngelis et al., 1992 and Heeger, 1992). The excitatory thalamic inputs are therefore normalized (divided) by a signal proportional to contrast. Normalization models have been highly successful in explaining many of the contrast-dependent, nonlinear properties of simple cells and will be considered below in more detail. One central driving force for inhibition-based models of cortical computation has been how well they can account for all

of the simple cell’s response nonlinearities (Carandini and Heeger, 2012). Aside from pharmacological experiments selleck kinase inhibitor showing a degradation of orientation selectivity under GABAA blockade,

however, direct experimental evidence for strong cross-orientation inhibition in cat V1 is equivocal. Intracellular recording of membrane potential (Vm) in simple cells shows little hyperpolarization in response to nonpreferred stimuli (Ferster, NSC 683864 price 1986). Measurements of Vm alone, however, cannot rule out the presence of shunting inhibition; an increase in membrane conductance with a reversal potential at rest would generate no hyperpolarization yet would reduce the effectiveness of excitatory current in depolarizing the membrane. Detecting the presence of shunting inhibition requires injecting current into a cell while presenting visual stimuli to move the membrane potential away from the reversal potential of inhibitory synapses. Such experiments suggest that inhibition in simple cells has the same preferred orientation and tuning width as excitation (Anderson et al., 2000, Douglas et al., 1995, Ferster, 1986 and Martinez et al., 2002; though see Monier et al., 2003). Overall, it appears that whatever shunting inhibition

is present at the nonpreferred orientation is too small to support the inhibitory models of orientation tuning. Additional evidence that visually selective synaptic inhibition others does not contribute directly to shaping orientation selectivity comes from experiments in which visually evoked action potentials in cortical cells are suppressed. During inactivation, either by cooling (Ferster et al., 1996) or by electrical stimulation (Chung and Ferster, 1998), orientation selectivity of the remaining excitatory input, the majority of which probably arises from the LGN, changes little. That is, the LGN inputs alone generate membrane potential responses that are as well tuned for orientation as the inputs from the fully functioning cortical circuit. These results give rise to an apparent contradiction. The feedforward input to simple cells is probably organized very much as Hubel and Wiesel proposed but apparently fails to account for many properties of simple cells.