Similar to primates with damage

to dorsolateral prefrontal cortex, rats with mPFC damage often show deficits in tasks requiring a delayed response (e.g., Horst and Laubach, 2009). The functional similarity between rodent mPFC and primate dorsolateral prefrontal cortex is further bolstered by demonstrations that both exhibit persistent cellular activity during delay periods that is selective for a prior or upcoming target location Protease Inhibitor Library ic50 (Baeg et al., 2003; Batuev et al., 1990; Funahashi, 2006). The idea that mPFC is specialized for working memory, however, has been undermined by recent findings. First, some of the most compelling evidence that mPFC plays a role in working memory are studies demonstrating that performance of rats with mPFC lesions gets worse with longer retention delays. However, in some of these studies, delay length is confounded with task novelty (Gisquet-Verrier and Delatour, 2006). In one example, mPFC-lesioned rats trained using a 5 s delay show impairment when switched to a 20 s delay (Delatour and Gisquet-Verrier, 1999); however, rats trained from the beginning on a randomly shuffled range of delays fail to show deficits (Gisquet-Verrier et al., 2000). Second, neurons in mPFC are highly selective to slight changes in position or trajectory (Cowen and McNaughton, 2007; Euston and McNaughton, 2006; Fujisawa et al., 2008). It is difficult to rule out the possibility that some, if

LEE011 not all, delay-related neural activity is entirely reflective of an “embodied memory” strategy involving differential behavior during the delay, rather than working memory per se. Indeed, it has been suggested that the primary deficit in rats with mPFC lesions is not information storage but rather the implementation of mediating strategies (Chudasama and Muir, 1997). Finally,

working memory in some studies is confounded with memory for the rules of the task (i.e., reference memory). As an illustration, Touzani et al. (2007) trained mice on a spatial win-shift task in which the correct choice depended on which maze arm was rewarded two trials back. Consistent with the hypothesis that mPFC supports working memory, mice with mPFC lesions were incapable of acquiring this task. However, mice given mPFC injections of a protein synthesis blocker after each daily training oxyclozanide session were also impaired. The lack of treatment during the task reduces the likelihood of interference with working memory. Instead, the impairment is likely due to disruption of consolidation which precluded acquisition of the task rules. In summary, many studies of working memory implicate the mPFC. Unfortunately, it is often difficult to determine whether the observed deficits are due to a breakdown in trial-specific working memory, mediating strategies, or a deficit in reference memory. Despite these concerns, a few well-controlled studies do support a role for rodent dorsal mPFC in working memory for actions.