PT - JOURNAL ARTICLE AU - Hanif, Sadiyah AU - Sclar, Mia AU - Lee, Jinah AU - Nichols, Caleb AU - Likhtik, Ekaterina AU - Burghardt, Nesha S. TI - Social Isolation During Adolescence Differentially Affects Spatial Learning in Adult Male and Female Mice AID - 10.1101/2024.07.31.606027 DP - 2024 Jan 01 TA - bioRxiv PG - 2024.07.31.606027 4099 - http://biorxiv.org/content/early/2024/08/01/2024.07.31.606027.short 4100 - http://biorxiv.org/content/early/2024/08/01/2024.07.31.606027.full AB - Social isolation is a risk factor for cognitive impairment. Adolescents may be particularly vulnerable to these effects, because they are in a critical period of development marked by significant physical, hormonal, and social changes. However, it is unclear if the effects of social isolation on learning and memory are similar in both sexes or if they persist into adulthood after a period of recovery. We socially isolated male and female 129Sv/Ev mice throughout adolescence (post-natal days 29-56), provided a 2-week re-socialization recovery period, and then tested spatial learning and cognitive flexibility in the active place avoidance task. After behavioral testing, mice were injected with 5’-bromo-2’-deoxyuridine (BrdU) so that lasting effects of social isolation on cell proliferation in the dentate gyrus could be examined. We found that in males, isolation led to a modest impairment in the rate of initial spatial learning, whereas in females, initial learning was unaffected. However, when the location of the shock zone was switched during the conflict variant of the task, cognitive flexibility was impaired in females only. Similarly, social isolation reduced cell proliferation in the ventral dentate gyrus only in females. Together, these findings indicate that social isolation during adolescence differentially impairs spatial processing in males and females, with effects that persist into adulthood.Competing Interest StatementThe authors have declared no competing interest.