With inhibition increasing concomitantly with the number of active afferents (for example through the progressive recruitment of feedforward inhibitory neurons), on the other hand, the recruitment of the neuronal population occurs in a progressive manner over a much wider range of inputs (Liu et al., 2011 and Pouille et al., 2009). Through the concomitant increase of excitation and inhibition, neuronal populations, or individual neurons (Liu et al., 2011) can thus differentially represent a larger range and number of combinations of afferent inputs. Normalization is a basic cortical computation through which the excitability of cortical

neurons changes in a manner that BIBF 1120 in vivo is inversely proportional to the overall activity level of the network (Heeger, 1992). It can account for several properties of cortical sensory processing, ranging from cross orientation suppression in the visual system (Freeman et al., 2002), to the modulation of sensory responses with attention (Reynolds and Heeger, 2009). The potential involvement of inhibition in cortical normalization is debated (Katzner et al., 2011) and needs to be elucidated. Furthermore, while the role of inhibition

in gain modulation, another basic cortical operation, is better established, the exact contribution of the various inhibitory circuits to this operation still needs EX 527 mouse to be assessed. A basic property of cortical neurons is that particular features of sensory stimuli preferentially drive the spike output of individual cells. For example, neurons in visual cortex can fire selectively to visual stimuli that have a particular orientation or direction (Figure 2A). Stimulus selective responses are observed in cortical regions devoted to all sensory modalities and understanding the mechanisms governing this tuning

of responses to preferred stimuli is critical for unraveling how the cortex represents sensory information. Since the selectivity to certain stimuli (e.g., orientation tuning) emerges for the first time in the cortex, (i.e., it is not present in any of the neurons along the chain that conveys the signal from the sensory interface to the cortex), cortical circuitry must contribute to generating this stimulus selectivity (Hubel and Wiesel, 1962). What role does synaptic inhibition play in the 4-Aminobutyrate aminotransferase tuning of cortical neurons to sensory stimuli? Pharmacological blockade of GABAA receptors reduces the stimulus selectivity of neurons in a variety of sensory cortices (Katzner et al., 2011, Kyriazi et al., 1996, Poo and Isaacson, 2009, Sillito, 1979 and Wang et al., 2000). However, the mechanisms by which synaptic inhibition regulates cortical tuning have been a source of debate. One popular idea follows from studies of lateral inhibition in the retina, in which stimulation in the receptive field center of a photoreceptor elicits excitation and stimulation in the surround evokes inhibition (Hartline et al., 1956).