In each experiment, stimulus position and strength was adjusted to elicit both stimulus-evoked spiking in the presynaptic cartwheel cell and feed-forward inhibition Olaparib in the post-synaptic fusiform neuron. Parallel fiber stimulus-evoked spiking in the presynaptic cartwheel was slightly changed in the absence of background spiking, with a lower probability of spiking on the first stimulus compared to the background spiking condition (compare Figure 8B, middle traces). Complex spikes were also sometimes more readily elicited by stimuli applied on a background of spontaneous firing. This can be attributed to
differences in cartwheel excitability at the different levels of bias current injection. More importantly, the outward component of the postsynaptic fusiform responses to Androgen Receptor Antagonist the second stimulus in the train was
significantly enhanced when the presynaptic cartwheel did not spike spontaneously in all cartwheel-fusiform pairs tested (compare bottom traces in Figure 8B; summary for 1.4 to 6.6 Hz background presynaptic firing rates in Figure 8C; stim 2 mean outward charge with background firing: 1388 ± 208 pA∗ms, no background firing: 2520 ± 366 pA∗ms, p < 0.05, n = 4 pairs). Total charge measurements from traces created by subtracting averaged fusiform currents obtained during background spiking in patch-clamped presynaptic cartwheels from those Adenosine recorded without presynaptic background firing (see example
Figure 8D) demonstrated a clear enhancement of outward charge following the second stimulus (Figure 8E; stim 2 1173 ± 357 pA∗ms). Thus, changing cartwheel spontaneous spiking activity by intracellular current injection alone was sufficient to alter parallel fiber-evoked feed-forward inhibition. In fact, the change in outward current following the second stimulus was remarkably similar to that observed previously in response to NA (compare Figures 1F, 6D, and 8B). These results support the idea that NA enhances feed-forward inhibition by indirectly relieving cartwheel synapses from depression through elimination of spontaneous action potential firing in a small number of connected presynaptic cartwheel cells. In contrast to the effects of NA, the response to the third stimulus was unchanged between the presynaptic background spiking versus no spiking conditions (Figure 8B; outward charge with background firing: 1149 ± 494 pA∗ms, no background firing: 1317 ± 434 pA∗ms, p = 0.14, n = 4 pairs). However, this likely reflected limitations of our experimental approach. In the paired recording experiments shown in Figure 8, parallel fiber stimuli were adjusted to evoke presynaptic cartwheel spikes reliably by the second stimulus in the train under both background spiking and no background spiking conditions.