NSC PhD Thesis Defense Seminar: Michele Saul

Changes in Exploratory Behavior and Cell Proliferation in the Amygdala Following Repeated Variable Stress in Male Rats: Focus on Adolescence

Monday, April 7

11:00 AM12:00 PM MC 3-7619 (Upper Auditorium)

Professors Julie Fudge, M.D. and Dana Helmreich Ph.D.


Adolescence is a developmental stage characterized by changes in exploratory behavior and neural organization. The amygdala, a key structure in the temporal lobe, is important for mediating exploratory behaviors, and continues to undergo plastic changes during adolescence. Stressful events can cause long-lasting changes in both exploratory behavior and brain development, suggesting that the adolescent amygdala may be affected. In these studies I examined whether a repeated variable stress (RVS) in male rats influenced exploratory behavior and a unique form of amygdala plasticity-- cellular proliferation-- focusing on adolescent animals.

In Aim 1, I compared the effects of RVS exposure in adolescent and adult rats on exploratory behavior six weeks later. Exploratory behavior in a novel anxiogenic, but not an anxiolytic, environment was significantly decreased in both age groups.

In Aim 2, I quantified the number of dividing cells in the amygdala of adolescent and adult animals, assayed using bromodeoxyuridine (BrdU) and immunocytochemical expression of neural markers. Normal adolescent rats showed 4-5 times more dividing cells in the amygdala than young adult animals. BrdU pulse-chase studies indicated that at least a portion of cells divide locally in the adolescent amygdala, leaving open the possibility that dividing cells are also migrating in. Further characterization with neural markers showed that BrdU-labeled cells do not show the developmental profile of typical neuronal precursors.

Finally, in Aim 3, I determined how RVS, which significantly altered exploratory behavior (Aim 1), influences cell proliferation/survival in the adolescent amygdala. Adolescent rats were administered RVS, injected with BrdU, and sacrificed either 24 hours or 10 days later. In stressed animals, the number of BrdU-positive cells significantly decreased 10 days post-BrdU (12 days post-RVS), but did not change 24 hours post-BrdU (2 days post-RVS). This suggests that RVS exerts effects over a delayed time course, possibly through apoptosis or cell cycle arrest.

In sum, RVS exposure decreases exploratory behavior in a novel anxiogenic environment and has delayed consequences for the number of dividing cell in the adolescent amygdala. RVS-induced behavioral changes may correlate with cell proliferation reduction, suggesting a potential anatomical link between amygdala plasticity and future behavior in anxiogenic environments.