Figure 2.

Chemogenetic inhibition of direct pathway striatal neurons (dMSNs) reduces neuronal activity. A, (Top) Illustration of the intersectional viral vector approach: A Cre-recombinase (Cre)-dependent AAV vector expressing hM₄Di was injected into the dorsomedial striatum and a retrograde CAV2-Cre virus was injected into the substantia nigra (SN). (Bottom) Viral spread is depicted in red. Dark shading indicates areas of expression common to all animals and light shading indicates areas of expression that varied across animals. B, Representative sections of mCherry-tagged hM₄Di immunofluorescence in the striatum (top) and in terminals in the SN (bottom) at ~4 months following viral infusions. Scale bar, 50 μm C, Representative section of GCaMP6m fluorescent expression in dMSNs following viral infusion. Scale bar, 20 μm. D, Representative calcium events (measured as ΔF/F) in dMSNs at baseline (top), following 10 μm CNO (middle) and following CNO washout (bottom). E, Calcium events were significantly reduced in dMSNs following CNO exposure (grey bar) compared to ACSF (white bar). **p=0.01 vs. baseline. Black dots represent data points of individual animals. N=6.