HIV-1 Tat exposure disrupts the inhibitory pre- and post-synaptic colocalization in the ACC. After 8 weeks of Tat exposure, excitatory and inhibitory synaptic markers were assessed within the PFC/ACC. In the whole PFC, 8 weeks of Tat induction decreased inhibitory pre- and post-synaptic proteins Syt2 and gephyrin, respectively, and increases GAD67, which is involved in the synthesis of GABA, as measured by immunoblotting (A–B). Representative images of IHC stained ACC neurons (C–D). Colocalization of inhibitory pre- and post-synaptic proteins Syt2 (red) and gephyrin (green), respectively, along pyramidal neuron dendrites indicated by the marker MAP2 (blue) in layer V of the ACC in Tat(−) (C) and Tat(+) (D) mice. Tat induction decreased Syt2 and gephyrin colocalization in layers II/III and V of the ACC after 8 weeks of DOX administration as measured by the overlap coefficient, the ratio of colocalized to non-colocalized pixels (E). Data are presented as mean ± SEM; n = 4–6 mice per group; ∗p < 0.05 vs Tat(−) mice; #p < 0.05 main effect of ACC layer; ↑ indicate colocalized inhibitory puncta; scale bar = 10 μm.