Here, we review growing evidence suggesting that new neurons in BLZ945 cost both the DG and OB contribute to pattern separation. Although the general pattern of afferent and efferent connectivity of new neurons in the DG recapitulates that of developmentally generated

dentate granule neurons, new neurons exhibit distinct physiological properties relative to mature neurons during a specific window of their maturation. Specifically, young 4- 8-week-old adult-born neurons show greater synaptic plasticity and, increased excitability (see Ming and Song, 2011, this issue of Neuron). These features of young adult-born neurons may be critical for their recently discovered role in pattern separation ( Figure 1). Clelland and colleagues used a two-choice touch screen spatial discrimination

task and a delayed nonmatching to place radial arm maze task to first demonstrate ATM inhibitor the impact of blocking hippocampal neurogenesis on spatial pattern separation (Clelland et al., 2009). In both tests, the correct choice that mice were required to make relied on discrimination of small or large spatial separations. Consistent with previous studies using DG lesions, the authors found that blockade of adult hippocampal neurogenesis by hippocampal x-irradiation impaired the animal’s ability to make fine, but not large, spatial discriminations. More recently, Sahay and colleagues used a contextual fear discrimination learning task, previously shown to require pattern separation in DG, to test whether new neurons are required for distinguishing between similar contextual representations (Sahay et al., 2011). The authors found that hippocampal x-irradiated mice exhibited similar levels of freezing behavior in both the shock associated

training context and a similar no-shock “safe” context, unlike controls that learned to discriminate between the two contexts (X-ray; Figure 1). A second study using the same click here contextual fear discrimination learning task yielded analogous results (Tronel et al., 2010). Together, these studies show that new neurons are required for pattern separation in three different DG dependent behavioral paradigms and raise the possibility that increasing adult hippocampal neurogenesis may enhance pattern separation. To directly address this possibility, Sahay and colleagues developed a genetic strategy to selectively increase adult neurogenesis (Sahay et al., 2011). In the contextual fear discrimination learning task, mice with more functionally integrated adult-born dentate granule neurons (iBax mice; Figure 1) were better at distinguishing between two similar contexts. These results indicate that increasing adult hippocampal neurogenesis is sufficient to improve pattern separation.