The IPSC scaled with, and dominated, the EPSC across the entire range of stimulus intensities (Figure 3E). We also determined the laminar organization of the recurrent excitatory and inhibitory synaptic inputs onto layer II pyramidal cells using focal illumination along the cell’s apical-basal axis in the presence of TTX/4-AP (Petreanu et al., 2009). These experiments indicate that pyramidal cells receive the majority of their recurrent excitatory input onto their proximal apical dendrites in layer Ib, whereas feedback inhibition is preferentially recruited by their axons projecting through see more layer III (Figure S3). How do these recurrent circuits shape the response

of piriform neurons to bulbar inputs? We paired a brief train of electrical LOT stimuli that mimics the burst firing of a mitral cell to odorant stimulation (Cang and Isaacson, 2003 and Margrie and Schaefer, 2003) with a brief train of light pulses in MEK inhibitor the piriform cortex (both stimuli, 5 pulses at 40 Hz; i.e., a 100 ms burst) and recorded the responses in pyramidal cells in current clamp. The stimulus strengths were adjusted to evoke spiking in 10% of the trials when either stimulus was presented alone (probability of spiking was 0.10 ± 0.38 following electrical stimulation of the LOT and was 0.10 ± 0.054 with light activation

of piriform; n = 6). In contrast to the low probability of spiking when LOT or piriform was activated alone, action potentials were evoked in 90% of the trials (0.90 ± 0.056) when the two inputs were presented simultaneously (Figure 4A). We next examined the effect of altering the temporal relationship between the pairing of bulbar and recurrent inputs. No increase in spiking was observed when the onsets of the two 100-ms-long bursts of stimuli were 150 ms apart. However, when the LOT train was delivered

100 ms before the piriform train, such that the last LOT-evoked input coincided with the first light-evoked input, the cell fired action potentials in 75% of the trials (0.75 ± 0.098; Figures 4B and 4C). In contrast, no enhancement in spike firing was observed aminophylline when the piriform train arrived 100 ms before the LOT input (0.20 ± 0.073; unpaired t test versus LOT alone, p = 0.423; versus PCx alone, p = 0.315; Figures 4B and 4C). We then examined the role of inhibition in this pairing paradigm by repeating these experiments in the presence of GBZ and the GABAB antagonist, CGP55845. Blocking inhibition broadened the time window over which spiking could be enhanced by pairing the inputs (Figure 4C). Furthermore, the efficacy with which the pairing of the inputs enhanced the response was less dependent on the order in which the two inputs were presented (skewness of control distribution, 0.64 ± 0.17, n = 6; skewness of distribution in GBZ, 0.21 ± 0.04, n = 4; unpaired t test, p < 0.05).