These data suggest that some, but not all, glutamatergic inputs t

These data suggest that some, but not all, glutamatergic inputs to the VS affect responses evoked by other inputs by way of heterosynaptic suppression. As burst PFC stimulation activates VS local inhibitory processes (Gruber

et al., 2009b), it is possible that local GABA neurotransmission contributes to the heterosynaptic suppression we report here. To assess this possibility, we included 200 μM picrotoxin in the intracellular solution for 22 cells from 15 adult male rats. As an open-channel blocker at the GABAA receptor, picrotoxin can antagonize GABAA signaling when applied outside or inside the cell membrane (Akaike et al., 1985; Cupello et al., 1991; Inomata et al., 1988; Metherate and Ashe, 1993). We found that the presence of picrotoxin in

the recording pipette impacted the baseline properties of recorded Buparlisib mouse MSNs. MSNs treated with picrotoxin had similar resting potentials (−84.8 ± 7.6 mV), up-state frequency (0.7 ± 0.2 Hz), and up-state duration (470.8 ± 105.9 ms) to untreated cells. The up-state amplitude, however, was altered by the presence of picrotoxin (−66.6 ± 6.8 mV; t(67) = 2.7; p < 0.01). Furthermore, the proportion of silent MSNs was reduced following picrotoxin treatment (7/22, 32%), and the spontaneous firing rate of active cells was enhanced relative to untreated cells (3.5 ± 3.5 Hz, range, 0.02–10.6 Hz; t(31) = 2.8; p < 0.01; Figure 5A). This increase in baseline firing activity suggests that picrotoxin relieved some tonic inhibition normally exerted onto VS MSNs. To assess whether GABAA antagonism reduced the PFC-driven suppression

of the fimbria-evoked EPSP, we subjected picrotoxin-treated cells to the stimulation protocol described above. Picrotoxin did not significantly alter the F1-evoked EPSP, which had an amplitude of 8.5 ± 6.4 mV and a time to peak of 28.8 ± 6.9 ms. In the presence of picrotoxin, PFC train stimulation evoked sustained depolarizations similar to those elicited by the train in the absence of picrotoxin; however, a greater percentage of MSNs fired action potentials during the PFC train (6/12; 50%). Following picrotoxin administration, the nearly amplitude of the F2-evoked response 50 ms after the PFC train was still reduced relative to that of the F1-evoked response (t(11) = 2.4; p < 0.05; Figures 5C and 5D). Although this difference appeared to be driven by one cell in particular, the amplitude of the F1 response in this cell was not identified as an outlier by the fourth spread test ( Hoaglin et al., 1983), so we included it in the analysis. However, the magnitude of PFC-evoked heterosynaptic suppression differed following PTX administration compared to the magnitude of suppression under baseline conditions. The PFC train reduced F2-evoked responses by 81.3% ± 15.4% in the absence of picrotoxin, whereas in the presence of picrotoxin, the magnitude of suppression was reduced to 49.6% ± 52.2%. The median magnitudes of suppression without and with PTX were 75.9% and 67.

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