Fig. 4. Inactivating vHC→loPFC projections weakens goal-directed response selection.

(A) Experimental timeline. Note that the DREADDs ligand CNO was administered immediately following instrumental contingency degradation. Response preferences were tested over the following 2 days when mice were drug-free. (B) Retro-Cre in the loPFC (blue), combined with a Cre-dependent Gi-DREADD in the vHC (red), was used to inactivate vHC→oPFC projections. Spread of viral vectors in the loPFC and vHC is drawn in the left hemispheres on images from the Mouse Brain Library (Rosen et al., 2000), and representative infusions are shown at right. (C) Mice were trained to nose poke for food reinforcers. “FR1” and “RI” denote the schedules of reinforcement. All mice acquired the responses during training without group differences. (D) Inactivation of vHC→loPFC projections impaired the ability of mice to generate response preferences based on the likelihood of reinforcement. (E) Impairments were persistent, detectable across several time bins and 2 test days, n = 10–11/group. Bars represent means ± SEMs. Symbols in C and E represent means + SEMs; otherwise, symbols represent individual mice. *p = 0.03 main effect of group; #p = 0.01 vs. 1 (1 reflects no change). This experiment was conducted in 2 independent cohorts of mice (for interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).