Abstract
Flexibility in using different learning strategies was assessed in two different inbred strains of mice, the C57BL/6 and DBA/2 strains. Mice were trained sequentially in two different Morris water maze protocols that tested their ability to switch their learning strategy to complete a new task after first being trained in a different task. Training consisted either of visible platform trials (cued training) followed by subsequent hidden platform trials (place training) or the reverse sequence (place training followed by cued training). Both strains of mice showed equivalent performance in the type of training (cued or place) that they received first. However, C57BL/6 mice showed significantly better performances than DBA/2 mice following the switch in training protocols, irrespective of the order of training. After completion of the switched training session, levels of cAMP response element-binding protein (CREB) and phosphorylated CREB (pCREB) were measured in the hippocampus, striatum and prefrontal cortex of the mice. Prefrontal cortical and hippocampal pCREB levels differed by strain, with higher levels found in C57BL/6 mice than in DBA/2 mice. No strain differences were observed in the medial or lateral region of the dorsal striatum. These findings indicate that the engagement (i.e., CREB signaling) of relevant neural structures may vary by the specific demands of the learning strategy, and this is closely tied to differences in the flexibility of C57BL/6 and DBA/2 mice to switch their learning strategies when given a new task.
Highlights
Different neural systems can be recruited during learning, depending on whether place/spatial or cued/response strategies are used to navigate a complex environment (McDonald and White, 1994; Packard and McGaugh, 1996; Hartley et al, 2003)
The differences between the two strains might reflect a superior ability of C57BL/6 mice to switch their learning strategies. To investigate this issue further, the present study directly examined strain differences in the ability to switch learning strategies in the Morris water maze and in cAMP response element-binding protein (CREB) and phosphorylated CREB (pCREB) levels in the hippocampus, striatum, and prefrontal cortex, which were used as indices of the engagement of these areas in response to specific training sequences (Colombo et al, 2003; Dalley et al, 2004; Floresco et al, 2008)
C57BL/6 Mice Showed Superior Performance in the Learning Strategy-Switching Task Compared With DBA/2 Mice
Summary
Different neural systems can be recruited during learning, depending on whether place/spatial (place) or cued/response (cued) strategies are used to navigate a complex environment (McDonald and White, 1994; Packard and McGaugh, 1996; Hartley et al, 2003). Recent studies have revealed interactions between the two systems and have implicated the prefrontal cortex in switching of learning strategy (Arias et al, 2014) Both C57BL/6 and DBA/2 mice are frequently used as the background strains of genetically modified mice in studies that are focused on the identification of molecular mechanisms critical for learning and memory function (Brooks et al, 2005; Mishina and Sakimura, 2007). C57BL/6 mice perform significantly better than DBA/2 mice in hippocampal-dependent tasks, such as place learning in the Morris water maze test or contextual fear conditioning (Paylor et al, 1993, 1994) In addition to these behavioral differences, strain differences in the functional neuroanatomical and neurochemical systems that support these behaviors have been reported. Despite hippocampal differences between two inbred mice, other studies have reported no differences in performance between C57BL/6 and DBA/2 mice on hippocampus-dependent tasks (Ammassari-Teule and Caprioli, 1985; Owen et al, 1997; Brooks et al, 2005; Middei et al, 2007)
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