Regulation of actions and habits by ventral hippocampal trkB and adolescent corticosteroid exposure
Fig 5
Overexpression of truncated trkB induces habits, makes them harder to “break,” and causes depression-like behavior.
(a) We infused a lentivirus expressing truncated trkB (Trkb.t1) or GFP into the vHC and CeA. Large (red) and small (white) infusion sites are represented on images from the Mouse Brain Library [27]. All infusion sites are described in S3 Fig. At bottom right, representative lentiviral GFP expression in the CeA is shown (at gray arrows). The external capsule is highlighted in red, and the image is intentionally overexposed. (b) In Trkb.t1-expressing mice, p-ERK42/44 immunoreactivity was diminished at the infusion site. n = 7–8/group. (c) All mice acquired the instrumental responses. Response acquisition curves represent both responses/min. (d) Trkb.t1 in the vHC and CeA blocked sensitivity to instrumental contingency degradation. Thus, selective Trkb.t1 overexpression recapitulated the long-term effects of adolescent CORT exposure. n = 6–8/Trkb.t1 group; total control = 23. (e) Another group of mice was first trained using a fixed ratio schedule of reinforcement. Then, to build on our findings reported in (d), an RI schedule of reinforcement was applied, with no interruption in training and no differences in responding between groups. (f) In reaction to repeated instrumental contingency degradation training, control mice inhibited a response that was unlikely to be reinforced, their habits “breaking” (“degraded contingency,” right). By contrast, mice with vHC Trkb.t1 failed to inhibit responding. Response rates associated with an intact contingency were unaffected (left). Response rates are represented on 2 plots in the interest of clarity but were compared together by ANOVA. n = 9–10/group. (g) Finally, vHC Trkb.t1 overexpression also decreased responding on a progressive ratio schedule of reinforcement in adulthood, again recapitulating the long-term effects of adolescent CORT exposure. n = 9/group. Bars/symbols = means + SEMs, * p < 0.05, ** p ≤ 0.004. Raw data for this figure can be found in S1 Data. CeA, central nucleus of the amygdala; ERK42/44, Extracellular signal-Regulated Kinase 42/44; p-ERK, phosphorylated ERK; trkB, tyrosine kinase receptor B; trkB.t1, truncated trkB; vHC, ventral hippocampus.