During slice experiments, mIPSCs were recorded in the presence of 5 μM NBQX and 1 μM TTX to block glutamatergic transmission and spontaneous activity, respectively. At a holding potential of −80 mV, mIPSCs were easily visible in MSNs (Figures 5A and 5D). The majority of these events likely arise from FS interneurons,

which have high rates of spontaneous release (Bacci et al., 2003 and Xiang et al., 2002) and form more numerous proximal synapses on MSNs than other selleck cell types (Gittis et al., 2010 and Taverna et al., 2008). In saline-injected mice, the frequency of mIPSCs was significantly higher in D1 MSNs than D2 MSNs (p = 0.02; Figure 5H), mirroring the higher connection probability normally observed between FS interneurons and D1 MSNs (Figure 1A). Mice injected with 6-OHDA showed no significant difference in mIPSC amplitudes (Figures 5B, 5E, and 5G) but showed a nearly 2-fold increase in mIPSC frequencies selectively in D2 MSNs (p = 0.0007) (Figures 5C, 5F, and 5H). The lack of change in mIPSC amplitude distribution after dopamine depletion (and enhanced FS innervation) indicates that mIPSCs recorded from MSNs arise predominantly from FS inputs, both before and after dopamine depletion. The increase in mIPSC frequency selectively in D2 MSNs is consistent

with increased innervation from FS interneurons. However, given the lack of increase in uIPSC amplitude (Figure 1E), these data suggest that for any given FS-MSN Alectinib purchase pair, the number of synapses formed is stereotyped. Thus, pre-existing FS-MSN pairs were not significantly strengthened, whereas new FS-MSN pairs were connected, on average, by similar numbers of synapses as preexisting pairs. To determine whether changes

in inhibitory innervation persist beyond 1 week, we measured mIPSCs in mice 2 weeks and 1 month after injections. Similar to data at 1 week, we observed changes in mIPSC frequency (but not amplitude) selectively in D2 MSNs (Figure S3). In saline-injected mice, mIPSC frequency was higher in D1 MSNs than D2 MSNs. In 6-OHDA-injected mice, mIPSC frequency in D2 MSNs was significantly increased at 2 weeks (p < 0.0001) and 1 month 17-DMAG (Alvespimycin) HCl (p = 0.003). These data suggest that increased innervation of D2 MSNs by FS interneurons persists for at least 1 month. To probe how increased connections from FS interneurons to D2 MSNs can affect striatal function, we developed a simple model of the striatal microcircuit (Figure 6A). MSNs and FS interneurons were modeled as single-compartment neurons with intrinsic properties that matched experimental data (see Experimental Procedures). Individual FS interneurons connected to D1 and D2 MSNs with probabilities based on data from Figure 1 (connection probabilities in the control model network were 0.5 for FS-D1 MSNs and 0.