Dopamine enhances EPSP-spike coupling at moderate concentrations.

<p>A) Example trace illustrating the recording set-up used to test DA modulation of EPSPs during active network states. Up-states were evoked by stimulation of the hippocampus in PFC-Hipp-VTA co-cultures. After a minimum of 500 ms (but typically between 1000–1500 ms) into the Up-state, trains of EPSPs (15 pulses at 20 Hz, indicated by the red box) were evoked by local stimulation of afferents close to the neuron recorded in the PFC using the same neurons and stimulation parameters as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006507#pone-0006507-g007" target="_blank">Figure 7</a> for the Down-state (N = 10). B) Representative traces showing the effectiveness of EPSPs to induce action potential firing during the Up-state under the baseline (black trace) and 100 nM DA condition (red trace). The green trace shows the averaged synaptic response during the Down-state before DA application. C) Summary graph showing the overall increase in spike number during the period of synaptic stimulation C2) and the change in EPSP-spike coupling in the 100 nM DA condition (red symbols) over baseline (black symbols). The plot shows for each pulse in the train the probability that a spike occurred within 10 ms of the onset of the stimulation. In the 100 nM DA condition the probability that an EPSP evoked an action potential was generally increased across all pulses. The relative magnitude of this effect was greater at later pulses in the train, with pairwise comparisons showing significant increases in spike probability over baseline starting at the 4^th pulse. D) In contrast to the effects during synaptic stimulation, bath application of 100 nM DA had no significant overall effect on Up-state duration (top) or the number of spikes before local synaptic stimulation (during the first 500 ms of the Up-state). <i>Post-hoc</i> comparisons used paired t-tests after repeated measures ANOVA (Bonferroni-adjusted level of significance * <i>P</i><0.0033, and ** <i>P</i><0.00165). E) The low dose of 10 nM DA had no effect of EPSP spike-coupling during the Up-state, or the overall properties of the Up-state (the inserts show measures for total Up-state duration, top bar graph; or number of spikes during the period before local synaptic stimulation, bottom; n = 7). F) In contrast, the high concentration of DA (10 µM) significantly reduced both Up-state duration (top) and the number of spikes within the Up-state. Thus, under these conditions both the synaptic signal (c.f. Fig. 7) as well as the background network activity were reduced. For comparisons at all concentrations the same cells were used as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006507#pone-0006507-g007" target="_blank">Figure 7</a>. In the 10 µM DA condition one cell dropped out because the Up-states evoked by hippocampal stimulation were too brief to allow stimulation of EPSP trains during the Up-state.