Experiments were initiated by establishing a whole-cell recording from an FS interneuron, then testing its connectivity with as many neighboring MSNs as possible until the presynaptic interneuron was lost. Typically 1–6 (average 2.4) MSNs were sampled per interneuron. The probability of finding a synaptic connection between FS-D1 MSN pairs was not changed by dopamine depletion. Connection probability was 0.60 in saline-injected selleck chemicals llc mice (average distance between pairs, 113 ± 49 μm) and 0.53 in 6-OHDA-injected mice (average distance between pairs, 105 ± 50.1 μm) (p = 0.60) (Figure 1A). In contrast, dopamine depletion

significantly increased the probability of finding a synaptic connection between FS-D2 MSN pairs. In saline-injected mice, connection probability was 0.39 (average distance between pairs, 116 ± 46 μm) but was nearly 2-fold higher, 0.77, in 6-OHDA-injected mice (average distance between pairs, 101 ± 48 μm) (p = 0.0004). Changes in FS connectivity occurred rapidly after dopamine depletion, with increased connectivity to D2 MSNs already present at 3 days after dopamine depletion (Figures 1B and 1C). Importantly, the observed change in connection probability was not due to a difference in the number of healthy “patchable”

D1 versus Lumacaftor purchase D2 MSNs in the slice after dopamine depletion. In 6 slices from a total of two 6-OHDA-injected mice, we counted 43 ± 7 patchable D1 MSNs and 40 ± 8 patchable D2 MSNs surrounding FS interneurons. In 6 slices

from 2 saline-injected mice, we counted 43 ± 10 patchable D1 MSNs and 42 ± 6 D2 patchable MSNs surrounding FS interneurons. As shown in Figures 1D–1G, dopamine depletion did not change the properties of unitary inhibitory postsynaptic currents (uIPSCs) recorded in MSNs. Action potentials evoked in presynaptic FS interneurons with brief somatic current injections (5 ms, typically ∼1 nA) reliably elicited uIPSCs in postsynaptic MSNs (Figure 1D). Amplitudes of uIPSCs were similar from trial to trial for a given pair but varied widely across the population (Figure 1E). The amplitudes of uIPSCs were not significantly different across conditions (pD1 = 0.94; pD2 = 0.20, Wilcoxon). These data demonstrate that postsynaptic GABA receptors at FS-MSN synapses are not altered after dopamine Oxyphenisatin depletion. To determine whether aspects of presynaptic function were affected by dopamine depletion, action potentials were elicited in presynaptic FS interneurons at frequencies of 10, 20, 50, or 100 Hz (Figures 1F and 1G). Short-term dynamics were measured as the change in amplitude of uIPSCs that accumulated during trains of ten action potentials at each frequency. Synapses exhibited frequency-independent depression, to 20%–40% their initial amplitudes, across all frequencies tested. The extent of this depression was similar in D1 and D2 MSNs and did not differ significantly between saline- and 6-OHDA-injected mice (p > 0.05 at all frequencies) (Figure 1G).