, 2010 and Leutgeb et al., 2007; Figure 1D). Along these lines, while much of the behavioral literature arguing for a pattern separation function is consistent, there are also alternative explanations. Instead of studying the ability of animals to distinguish Vorinostat solubility dmso different input patterns concurrently,

the behavioral studies of the roles of the DG and neurogenesis in pattern separation have typically been designed to examine how animals’ responses to their present situation can be altered by their memories of the past input patterns (which are different from the current ones). Two types of strategies have been used in behavioral tasks for pattern separation. In some tasks, animals were trained to Selleck GS-7340 distinguish two input patterns, such as conditioned (CS+) and unconditioned (CS−) contexts. Specifically, initial training enabled the animals to generalize their conditioned responses to both CS+ and CS− contexts, and their ability to discriminate the CS+ and CS− contexts was subsequently tested through continuing reinforcement of the CS+ context but not the CS− context (McHugh et al., 2007 and Sahay et al., 2011).

It is possible that performance changes resulting from alterations in DG and/or neurogenesis may be due to defects in pattern separation, but it is also possible that other processes, such as inhibitory learning, may be involved. In other tasks, animals were trained also to learn one pattern and were subsequently tested, using a working memory framework, for their ability to discriminate a learned pattern from another pattern (Clelland et al., 2009, Creer et al., 2010, Gilbert et al., 2001, Hunsaker and Kesner, 2008 and Saxe et al., 2007). Paradigms using this type of task are also able to evaluate behavioral performance as a function

of the extent of input pattern differences such as by varying the distance of spatial location systematically in the cheeseboard spatial discrimination task (Gilbert et al., 2001), further supporting a relationship between the pattern separation ability and behavioral outcome. However, it remains difficult to rule out in these tasks that animals may solve the task using different neural pathways according to the degree of dissimilarity between the input patterns. For example, in the cheeseboard spatial discrimination task, lesions of CA1 did not affect the performance at any of five tested pattern separation degrees, suggesting that the task could be solved independent of the trisynaptic pathway (Gilbert et al., 2001). On the other hand, lesions of CA3 affect working memory in general, making it difficult to test whether pattern separation relies on CA3 outputs other than Schaffer collaterals (Gilbert and Kesner, 2006). Finally, there is a lack of a clear role for young neurons that would make them advantageous in the classic mechanism by which the DG provides separation.