Figure 1. Cre-ON and Cre-OFF Vectors Enable Targeting of Complementary Striatal Populations for Monosynaptic Rabies Virus Tracing.

(A) Complementary targeting strategy for labeling monosynaptic inputs to cocaine-activated (Cre-ON) or non-activated (Cre-OFF) DS neurons.

(B) Cre-ON and Cre-OFF expression systems for selective expression of TVA and RG.

(C) Labeling of monosynaptic inputs to either cocaine-activated (Cre-ON, left) neurons or non-activated (Cre-OFF, middle) neurons. Corticostriatal projection patterns are also assessed using RV as a traditional retrograde tracer ([RG]RV-ΔG-eGFP) that is taken up nonselectively at axon terminals in the DS (right).

(D-F) Fluorescence images of Arc-dependent tdTomato expression (red), RV-infected neurons (green), and DAPI (blue) in cocaine-exposed animals previously injected with either Cre-ON (D) or Cre-OFF (E) AAVs followed by monosynaptic RV, or with no AAVs and retrograde RV alone(F). Scale bar applies to (D-F).

(G-I) Insets of hatched squares in (D-F). Monosynaptic inputs to cocaine-activated DS neurons are labeled green, while all cocaine-activated neurons are labeled red. Coincident label (yellow) indicates cocaine-activated cortical neurons that form direct connections to the targeted DS neuronal population. Scale bar applies to (G-I).

(J-L) Retrograde label in mouse barrel cortex for Cre-ON (J), Cre-OFF (K), and retrograde RV(L) conditions. Scale bar applies to (J-L).

See also Figures S1 and S2.