LED illumination was restricted to a spot (∼150 μm diameter) and we compared the amplitude of IPSCs elicited when the photostimulus was over the GC layer versus when the illumination surrounded the glomerulus containing the dendritic tuft of the recorded mitral cell (filled with fluorescent indicator). Shifting the location of the photostimulus from the GC layer to the glomerular layer largely abolished light-evoked mitral cell IPSCs (Figure 3C; 4.0 ± 1.6% of GC layer

response, n = 6), indicating that cortically-evoked mitral cell inhibition 3 Methyladenine arises primarily from the GC layer. Taken together, these results are consistent with the idea that activation of cortical fibers is sufficient to elicit disynaptic inhibition onto mitral cells

that results from click here AMPAR-mediated excitation of GCs. Intriguingly, activation of cortical feedback projections also elicited feedforward IPSCs in GCs. GABAAR-mediated IPSCs (recorded at the reversal potential for excitation) followed light-evoked EPSCs with a disynaptic delay (3.5 ± 0.5 ms, n = 14; Figures 4A1 and 4A2) and were abolished following application of glutamate receptor antagonists (Figure 4A3). Short-latency feedforward inhibition plays an important role in regulating time windows for excitation (Pouille and Scanziani, 2001). Indeed, in current clamp recordings (Vm = −60 mV) of cells with a mixed EPSP-IPSP, blocking the disynaptic IPSP greatly prolonged the duration of cortically-evoked EPSPs (½ width = 6.5 ± 1.7 ms versus 58.4 ± 18.7 before and after gabazine, respectively) without effecting peak EPSP amplitude (110.4 ± 7.7% of control, n = 5, Figure 4B). Although the amplitudes PDK4 of light-evoked excitatory and inhibitory conductances were similar across the population

of recorded GCs (average excitation [GE] = 1.1 ± 0.3 nS, inhibition [GI] = 1.4 ± 0.3 nS, n = 42), the relative contribution of inhibition to the total conductance (GI/(GE + GI)) varied widely within individual cells (Figure 4C). Anatomical reconstruction of dye-filled GCs did not reveal an obvious correlation between cell morphology and the excitation/inhibition ratio (n = 7, data not shown). Heterogeneity in the relative amount of excitation versus inhibition received by individual GCs suggests that cortical feedback inputs could have diverse effects: activation of the same cortical fibers could cause a net increase in the excitability of some GCs while neighboring GCs are suppressed. We tested this idea by giving nearby (within 100 μm) GCs depolarizing current steps sufficient to elicit APs and interleaving trials with and without trains of light flashes. Indeed, we found that cortical fiber activation in the same region could either enhance or suppress AP firing in GCs (Figure 4D1).