HIV-1 Tat protein alters medial prefrontal cortex neuronal activity and recognition memory

Despite advancements in combined antiretroviral therapy, HIV-associated neurocognitive disorders (HAND) continue to affect 40–50% of people living with HIV. While neuroimaging studies have revealed HIV-1–induced alterations in cortical networks and brain macrostructures, how individual neurons in the medial prefrontal cortex (mPFC) are affected during recognition memory remains unclear. Using in vivo calcium imaging in an HIV-1 Tat transgenic mouse model, we examined mPFC neuronal activity during a novel object recognition memory task. Our findings show that HIV Tat expression reduces overall neuronal activity in Tat(+) mice without altering the number of activated cells. Moreover, distinct neuronal subpopulations are up- and downmodulated in both Tat(–) and Tat(+) mice depending on object exploration. Importantly, familiarity-driven increases in mPFC activity were disrupted by HIV Tat expression. These findings enhance our understanding of HAND-related cognitive deficits and may inform future pharmacological strategies aimed at restoring cognitive function.