Figure 2. Characterization of a Disynaptic (PV-NPY-MSN) Inhibitory Microcircuit.

(A) Striatal PV interneurons are fast-spiking interneurons (FSIs) that are characterized by a high firing frequency in response to depolarizing current injection (left). PV interneurons expressing ChR2 produced action potentials in response to blue light (right, 0.5 ms duration, 470 nm, 3 mW) with a latency of 0.3 ms (right, inset).

(B) Sample traces (average of 3 sweeps) of IPSC responses in MSNs, NPY-NGF, and NPY-PLTS cells after optical activation of PV interneurons.

(C) Mean evoked IPSC properties in MSNs and NPY interneurons after optical activation of PV interneurons. While the largest IPSC response magnitude was found to be in MSNs (n = 7), NPY-NGF cells (n = 9) produced IPSC responses with higher amplitudes (unpaired t-test, p = 0.02), larger areas (p = 0.015) and longer decay times (p = 0.018) compared to light-responsive NPY-PLTS cells (n = 5).

(D) Schematic model of microcircuitry of striatal PV interneurons coupled to MSNs both monosynaptically and disynaptically via NPY-NGF interneurons.

(E) Response of 49 MSNs recorded in vivo to optical stimulation in NPY-Chrimson mice. Left: The mean activity decreased during 5 s continuous light delivery (green bar). Middle: The change in firing rate varied with optical fiber output power (one-way ANOVA, F_4,192 = 7.7, p < 0.0001). Right: RMI distribution at 10 mW. The median RMI was significantly different from zero (signed-rank test, p < 0.0001). Data in (C) and (E) represent mean ± SEM.*p < 0.05;**p < 0.01; ****p < 0.0001.