LONG-TERM IMPACT OF SOCIAL ISOLATION DURING ADOLESCENCE ON ANXIETY-LIKE BEHAVIORS: IMPLICATION OF HIPPOCAMPAL NEUROGENESIS ​

Chronic stress is perceived as the enduring exposure to challenging situations exceeding an individual’s resources, leading to emotional disturbances. However, it can modulate brain activity and functions according to time-window of exposure. Adolescence is described as a period of vulnerability to environmental insults and of emergence of mental disorders, but the underlying mechanisms remain unknow. Due to its sensitivity to stress and role in emotion, hippocampal neurogenesis (HN) is a likely candidate: yet, further studies are needed to pinpoint the impact of adolescent stress in the sequential waves of HN occurring during and after stress exposure. To address this gap, we aimed to 1) determine the long-term effects of a social stress applied during adolescence on emotional behaviors (trait and state anxiety), and 2) identify the neurogenic processes involved. We developed a stress paradigm consisting of 2-weeks adolescent social isolation (ado-SI) from postnatal day (PND) 21 until PND35 in C57BL/6J mice. At adulthood, mice are subjected to a battery of tests to assess trait anxiety followed by an Elevated Plus Maze (EPM) performed after a Swim Stress to test for state anxiety. We found that the behavioral consequences of ado-SI emerge under baseline conditions, reflected in trait anxiety, and are further unmasked upon stress re-exposure, resulting in increased state anxiety. To understand the involvement of adolescent- and adult-dentate granule neurons, we targeted these populations and are currently looking at rate – cell survival, proliferation and maturation –, morphology – dendrites and axon - and functional relevance – recruitment during anxiety testing.