Figure 9. CXCL12 depends on Rac1 activation to rescue cognitive flexibility and dendritic spine density in the HIV-Tg rat.

(A) Inhibition of Rac1 activity blocked the ability of CXCL12 to positively enhance cognitive flexibility in an attentional set-shifting task. N = 9 for veh+veh, N = 9 for veh+CXCL12, N = 8 for NSC+veh, and N = 8 for NSC+CXCL12. (B) NSC23766 co-treatment significantly attenuated the rate at which animals reached criterion on the shift to cue phase as assessed by linear regression. N = 9 for veh+veh, N = 9 for veh+CXCL12, N = 8 for NSC+veh, and N = 8 for NSC+CXCL12, F_(3,32)=7.503, p=0.0006. (C) Blockade of Rac1 activation abrogated the effect of CXCL12 on overall dendritic spine density in HIV-Tg rats. N = 9 for veh+veh, N = 9 for veh+CXCL12, N = 8 for NSC+veh, and N = 8 for NSC+CXCL12, eight dendrites measured for each animal and averaged into single data point, **p<0.01, ***p<0.001. (D) CXCL12’s impact on thin spines was mitigated by co-treatment with NSC23766. N = 9 for veh+veh, N = 9 for veh+CXCL12, N = 8 for NSC+veh, and N = 8 for NSC+CXCL12, eight dendrites measured for each animal and averaged into single data point, **p<0.01, ***p<0.001. (E) NSC23766 prevented decreases in stubby spine density mediated by CXCL12 treatment. N = 9 for veh+veh, N = 9 for veh+CXCL12, N = 8 for NSC+veh, and N = 8 for NSC+CXCL12, eight dendrites measured for each animal and averaged into single data point, *p<0.05. (F) There was no significant relationship observed between overall dendritic spine density and trials to criterion on the set-shifting phase of the behavioral task. N = 12 animals, Pearson’s r = −0.2256, p=0.4808. (G) Thin spine density was negatively associated with the number of trials to criterion in the shift to cue phase of the behavioral task. N = 12 animals, Pearson’s r = −0.7787, p=0.0029.

Figure 9—figure supplement 1. Inhibition of Rac1 activation by NSC23766 does not alter performance on position discrimination or position reversal in HIV-Tg rats.