“Lateral” inhibition could occur if adjacent domains of sensory cortex (such as orientation columns within cat visual cortex or whisker maps in rodent barrel cortex) are tuned to different stimulus features—and inhibition in one cortical

subregion can be influenced by neighboring domains. While the necessary circuits for such lateral inhibitory interactions exist in cortex (Adesnik and Scanziani, 2010), determining their exact spatial extent and impact on sensory processing will require more work. Furthermore, in the visual, auditory, and olfactory cortices of rodents, stimulus selective responses selleck inhibitor occur despite the fact that cells tuned to particular stimulus features are spatially intermingled in a “salt and pepper” organization

(Ohki et al., 2005, Rothschild et al., 2010 and Stettler and Axel, 2009). A less literal form of lateral inhibition that does not require a two dimensional spatial mapping of stimulus features still applies to cortical tuning: namely, that synaptic excitation to a preferred stimulus Cytoskeletal Signaling inhibitor roughly shapes the tuning of a cell’s spike output and that tuning is further sharpened by robust synaptic inhibition in response to nonpreferred stimuli (Priebe and Ferster, 2008). This notion, however, has been challenged by intracellular recording studies in several cortical regions showing that in individual neurons the stimuli that generate the strongest excitation (preferred stimuli) can be the same as those generating the strongest inhibition (Figures 2A and 3B; Anderson et al., 2000, Liu et al., 2011, Mariño et al., 2005, Martinez et al., 2002, Tan et al., 2004, Tan et al., 2011, Wehr and Zador, 2003, Wilent and Contreras, 2005, Wu et al., 2008 and Zhang et al., 2003, but see Monier et al., 2003). Furthermore, Thymidine kinase as the stimulus gradually changes away from the preferred feature, both excitation and inhibition

decrease. In other words the tuning curves for excitation and for inhibition show considerable overlap. How then could inhibition sharpen the tuning of cortical neurons to the preferred stimuli? This can happen in several ways. First, it is important to note that the tuning curve determined through the spike output of a neuron is not equal to the tuning curve determined by recording the membrane potential of that neuron. Because only the strongest excitatory input received by a neuron sufficiently depolarizes the membrane to reach threshold for spike generation, (i.e., the “tip” of the tuning curve of the membrane potential), the spike output of the neuron is more sharply tuned than the underlying membrane potential (Figure 4), a phenomenon appropriately called “iceberg effect” (Carandini and Ferster, 2000 and Rose and Blakemore, 1974). In other words, the non-linearity of spike rate versus membrane potential sharpens the tuning of a neuron.