Inhibition, which interacts intimately with excitation, slows down saturation and increases the input dynamic range. This

leads to a sharpening of selectivity of membrane potential responses. Our results demonstrate that inhibition plays an indispensable role in the generation of sharp OS in mouse simple cells. The broad inhibition revealed in these cells suggests that different cortical circuits combine excitation and inhibition in unique ways to produce OS. In this study, we focused on simple cells since they have been thought as the group of neurons in which OS first emerges. Different from cats, in the mouse V1, neurons exhibiting conventional simple-type receptive fields (RFs) are much more abundant in layer 2/3 than layer 4 (Liu et al., 2009). With loose-patch recordings, which detect spike signals signaling pathway from patched neurons without affecting their intracellular milieu, we BKM120 clinical trial first examined OS of simple cells in layer 2/3. The On/Off spatial RF was mapped to determine the cell type, and the relationship between the RF structure and OS was determined. As shown in Figure 1A, the example neuron displayed a typical simple-cell RF with spatially segregated On and Off subfields. When tested with drifting sinusoidal gratings, the cell responded maximally to vertically oriented gratings (Figure 1B). The cell’s preferred orientation is similar to

the orientation perpendicular to the RF axis, which is defined as the line connecting the centers of On and Off subfields (see Experimental Procedures). A summary

of 34 simple cells (Figure 1C) indicates a strong correlation between the preferred orientation and the RF axis, consistent with previous observations in the cat V1 (Lampl et al., 2001). According to this result, the preferred orientation of a simple cell can be predicted rather precisely from its On/Off RF structure. Alanine-glyoxylate transaminase By whole-cell current-clamp recording with a K+ gluconate-based intracellular solution, we next compared OS exhibited in spiking responses with that in subthreshold responses (i.e., residual membrane potentials after filtering out spikes). As shown by an example cell (Figure 1D), robust membrane depolarization responses were evoked by gratings at all testing orientations, although significant spiking responses were only observed for two orientations. Therefore, the orientation tuning of postsynaptic potential (PSP) response was much weaker compared to that of spiking response, although the two types of response exhibited the same optimal orientation (Figure 1E). In a total of 24 simple cells, similarly we found that spiking and PSP responses in the same cell exhibited essentially identical preferred orientations (Figure 1F). The orientation selectivity index (OSI, see Experimental Procedures) of spiking response was positively correlated with that of PSP response (Figure 1G).