Fig. 4. VLO-selective Bdnf knockdown interferes with goal-directed action selection.

(a) A task schematic is shown. Mice are trained to generate two distinct responses. Then, the likelihood that one response will be reinforced is decreased. Preferential engagement of the remaining response during a probe test is interpreted as goal-directed action selection, while engaging both responses equivalently — despite contingency degradation — is codified as habitual behavior. (b) Bdnf was knocked down bilaterally in the VLO. Infusion sites are summarized on images from (60). Black represents the largest viral vector spread, and white the smallest. (c) Inset: Infusions resulted in decreased BDNF expression in homogenized VLO tissue. Mice were trained to nose poke for food reinforcers; Bdnf knockdown reduced response rates, particularly when the response requirement escalated from a fixed ratio 1 to random interval schedule (final 2 sessions). Rates represent total responses on both apertures. (d) Mice with Bdnf knockdown were also unable to select between actions that were more, vs. less, likely to be reinforced (non-degraded vs. degraded) following instrumental contingency degradation; instead, they engaged familiar habit-like response patterns, generating both responses equally. (e) BDNF expression in the downstream amygdala correlated with the degree of impairment following VLO-targeted Bdnf knockdown, with low BDNF associated with robust responding on the ‘degraded’ nose poke aperture. Amygdala BDNF expression was also reduced overall in mice with VLO-targeted Bdnf knockdown (inset). Symbols and bars represent means+SEMs, except in (e) where each symbol represents a single mouse.*p<0.05.