Figure 3. QA-induced mPFC damage affects the use of cognitively demanding spatial search strategies.

(a) Both sham (upper panel) and QA-injected animals (bottom panel) adopted a prominent use of spatial strategies during the acquisition phase of MWM learning (i.e., before the surgical procedure, white triangles). After surgery, sham mice quickly return to their use of spatial strategies (non-spatial and repetitive strategies as well as perseveration occur well below chance level). In contrast, QA-injected animals never regain their use of spatial strategies, and rather continue to rely on a mixture of other types of search strategies. Data are presented as means ± SEM. (b) Increase in the proportional use of different search strategies across 5 days of reversal learning (after surgery) in the sham-treated group. White bars illustrate the increasing use of spatial strategies, reaching a maximum on days 4 and 5. (c) Defects in spatial strategy use in QA-injected animals. These mice reached their maximal, more limited use of spatial strategies already on day 3, and continued to rely substantially on repetitive strategies. (d) Marked differences in the use of strategy subtypes between control and lesioned mice on the last reversal day. The figure compares between their last day of acquisition (upper left) and reversal (upper right). Number in the x axis corresponds to the different strategy subtypes as listed in Table 2 with (1) spatial direct; (2) spatial indirect; (3) focal correct; (4) scanning; (5) random; (6) focal incorrect; (7) chaining; (8) peripheral looping; (9) circling; (10) perseveration, only possible on reversal days. The bottom panel shows that sham animals almost exclusively used spatial strategies (spatial v. non-spatial: p < 0.001; spatial v. repetitive: p < 0.001; spatial v. perseveration: p < 0.001), whereas lesioned animals do not have a preference for any particular search strategy. However, perseveration was very low in both groups (spatial v. perseveration: p < 0.001).