Fig. 3. NGF activation of p75 and TrkA receptors differentially regulate firing patterns.

NGF activates both p75 and TrkA receptors in sympathetic neurons. Co-application of NGF with the TrkA blocker K252a, or the p75 blocking antibody REX was used to selectively activate each signaling pathway. A. Plots of spike output versus stimulus amplitude show that NGF with the TrkA antagonist (200 nM K252a, filled circles) resulted in a significant decrease in spike output compared to saline (black line) or NGF alone (gray line; n = 22, p < 0.01, Two Way ANOVA followed by the Tukey test). Application of NGF with the p75 function-blocking antibody (REX 1:700, open triangles) resulted in a significant increase in spike output compared to saline or NGF alone (n = 20, p < 0.01 Two Way ANOVA followed by the Tukey test). The REX antibody applied alone had no significant effect (gray squares, n = 28). B. A raster plot of spike times elicited with a 500 % of threshold stimulus shows that in NGF/K252a 85% of cells (18/21) fired 5 or fewer spikes occurring within the first half of the stimulus, showing a phasic pattern (n = 21, 4 trials each). C. A raster plot of spike times elicited with a 500 % of threshold stimulus showing that NGF/REX promoted tonic firing (n = 20, 4 trials each). D. We used the percentage of spikes occurring in the second half of the stimulus to provide a measure of phasic and tonic firing. A bar plot shows the percentage of spikes occurring in the second half of the stimulus for cell for the different treatment groups. Neurons in NGF and, to a greater extent, NGF/K252a fired fewer second-half spikes compared to saline (p < 0.05, all three groups different, Kruskall Wallace ANOVA on ranks followed by Dunn's test). NGF/REX caused a significant increase in second-half spikes compared to saline and NGF alone (p < 0.05, all three groups different, Kruskall Wallace ANOVA on ranks followed by Dunn's test). REX alone was not different from saline.