For example, enriched environments are generally thought to promote exploration and learning and may exert greater cognitive demands by requiring encoding of details and generation and maintenance of multiple nonoverlapping representations. Increased levels of adult neurogenesis following environmental enrichment may serve two adaptive functions. First, it may facilitate the faithful processing of the complex environment through enhanced pattern separation thereby also ensuring rapid recognition of such environments in the future (Kempermann, 2008). Second, it may prevent the DG from being overburdened with contextual information by rapidly transferring

memories out to the cortex (Kitamura et al., 2009).

In contrast, decreased neurogenesis due to stressful environments may lead to generalization of individual features and enable the organism to avoid similar situations Duvelisib in vitro by restraining exploration. For example, increased Autophagy Compound Library high throughput generalization in a hostile environment may be adaptive because it promotes avoidance of most potential threats. It should be emphasized that changes in neurogenesis are not required for acute responses to the environment for which other synaptic modifications in the DG may suffice. Instead, environment-dependent changes in neurogenesis may prepare the organism for novel habitats on longer time scales. Disruption in these normal adaptive regulations of neurogenesis may occur in pathological contexts resulting in excessive or impaired pattern separation (Figure 3). Excessive pattern separation may impede normal integration

of environmental information, as the individual will devote too much attention to individual contextual and sensory features at the detriment of the “big picture.” Behaviorally, this may manifest as cognitive inflexibility, increased preoccupation with minutiae, and unrestrained fixation on fine details as seen in autism spectrum disorders (Mottron et al., 2006 and Soulières click here et al., 2009) or obsessive-compulsive personality disorder (American Psychiatric Association, 2000). In contrast, impaired pattern separation may lead to excessive generalization, which would cause an organism to lump multiple contexts or items together even if the similarity between them is minimal. Such a maladaptive response may underlie the increased generalization of new “innocuous” experiences with previously encountered aversive events seen in individuals with panic disorder (Lissek et al., 2010) and post-traumatic stress disorder (PTSD) (Peri et al., 2000). For example, in somebody who developed PTSD as a result of 9/11, the simple sight of a plane flying over New York City may be sufficient to trigger a panic attack. In addition, impaired pattern separation has also been reported during aging and in individuals with mild cognitive impairment (Toner et al., 2009, Yassa et al., 2010a and Yassa et al., 2010b).