As with nonhuman primates, the activity of the PFC during the delay period of working memory tasks is altered in older adults. Indeed, an fMRI study revealed age differences in the pattern of activation of the lateral PFC that were dependent on the trial phase, with lower activation during

task delays and greater activation at the time of the probe in older adults (Paxton et al., 2008). These results suggest that aging may also affect delay neurons not only in monkeys Ku-0059436 nmr but perhaps in humans as well. The activity of OFC neurons has been characterized in young and aged rats while performing two different tasks, a delay-discounting task and a reversal task (Schoenbaum et al., 2006; Roesch et al., 2012). In a delay-discounting task, rats have the choice between a small immediate reward and a large reward delivered after a delay. In this task, aged rats were found to prefer the large reward regardless of the length of the delay whereas young rats were more prone to switch their behavior towards the small immediate reward as the delay increased (Simon et al., 2010). Using a delay-discounting task, Roesch et al. (2012) addressed whether there are age-related differences in the activity of OFC neurons in response to varying the length of delays. They found a higher prevalence of neurons responsive to long delay rewards in aged rats.

NU7441 While ~ 50% of reward-responsive neurons were active during short delays in aged rats, ~ 75% of the neurons fired preferentially to short delays in young rats (Roesch et al., 2012). There was no age difference in the proportions

of cells responding to large over small rewards (Roesch et al., 2012). Thus, aging appears to selectively affect OFC delay neurons. It is possible that age-related changes in plastic processes in OFC biased the older neurons from adapting their activity in a manner similar to that of the younger animals. This lack of adaptation of OFC cells may be responsible for the lack of willingness of older animals to change their behavior towards receiving a large reward in spite of the long delay associated with doing so. Aged rats are known for their behavioral impairments BCKDHA on reversal tasks (Schoenbaum et al., 2002; Mizoguchi et al., 2010). Whereas older rats are able to acquire discrimination problems at high levels of performance, some are impaired when contingencies are reversed. Because the OFC is critical for reversal performance, Schoenbaum et al. (2006) recorded neurons from this brain region in young and aged rats while they performed a go, no-go task with reversals. In this task, rats learned to associate pairs of odors predicting either a reward or an aversive fluid. Following presentation of a ‘go’ odor, rats learned to go to the food port to receive a reward. Following a ‘no-go’ odor, rats learned to avoid going to the food port where an aversive quinine solution was delivered.