3% ± 7.1% compared to baseline). The decomposition of the sound-driven increase in membrane conductance into excitatory and inhibitory components indicated that noise bursts elicited the opening of inhibitory conductances (5.7 ± 1.1 nS), associated with a smaller withdrawal of excitation (−0.4 ± 0.2 nS; Figures S2C–S2E). A similar pattern of inhibitory and excitatory conductance changes was evoked by photostimulation
of A1 (Figure 2B). We next directly tested the effects of GABA blockade on SHs. First, we blocked GABAA and GABAB receptor-mediated Selleck Forskolin inhibition by intracellularly perfusing neurons with picrotoxin (PTX) and cesium (Cs) ion. Great care was taken to minimize picrotoxin spillover, monitoring concurrent extracellular activity (Figure S4A). To check whether this manipulation was effective in blocking GABAergic inputs onto L2/3 s of V1, we examined the intracellular responses to local electrical stimulation (see Supplemental Experimental Procedures), which has been shown to evoke
robust inhibitory www.selleckchem.com/Wnt.html responses (Contreras et al., 1997 and Douglas and Martin, 1991). We found that intracellular PTX/Cs abolished the large hyperpolarizing responses observed upon microstimulation (Figure S4B; n = 11 from 5 mice; −11.4 ± 0.8 versus −1.5 ± 0.4 mV before and after intracellular perfusion, respectively, p < 0.001). SHs also vanished in most cells during intracellular perfusion with PTX/Cs (Figure 4B; n = 17 cells from 9 mice; −3.5 ± 0.3 versus −1.3 ± 0.4 mV, p < 0.01). Simultaneously recorded FP responses remained unchanged, however, indicating that the intracellular perfusion did not prevent SHs in neighboring cells (Figure S4C). Second, we blocked GABAA or GABAB receptors by topical application of gabazine or CGP52432, at concentrations that did not cause epileptiform activity (1.5 μM and 1 μM, respectively; Figure S4D–S4F). We
recorded 8 cells under gabazine, 15 cells under CGP52432 and 6 cells under a cocktail of both drugs. These experiments showed that SHs Phosphoprotein phosphatase are composed of an early, GABAA-IPSP and a late, GABAB-IPSP (Figure 4C). Gabazine left only a late component of SHs (Figure 4D, right plot; median onset latency: 161.5 ms), while blocking their early phase (Figure 4C, top; postsynaptic potential [PSP] peaks within 0–150 ms poststimulus: −3.4 ± 0.4 versus 1.4 ± 0.7 mV, p < 0.001 for post hoc test). Gabazine (either alone or in combination with CGP52432) unmasked a small excitatory response, indicating that acoustic stimulation also activates some excitatory synapses whose effects are masked by inhibition (6 out of 14 cells). CGP52432 reduced the late SH (Figure 4C, bottom plot; PSP peaks within 150–400 ms poststimulus: −2.5 ± 0.2 versus −1.1 ± 0.4 mV, p < 0.01 for post hoc test), thus shortening SHs (Figure 4E; median half-widths: 85.4 ± 8.0 versus 227.2 ± 19.5 ms in controls, p < 0.001 for post hoc test).