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

Despite advancements in combined antiretroviral therapy, human immunodeficiency virus (HIV)-associated neurocognitive disorder (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, it still remains unclear how individual neurons in the medial prefrontal cortex (mPFC) are affected during recognition memory. Using <i>in vivo</i> calcium imaging in an HIV-1 transactivator of transcription (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 and may inform future pharmacological strategies aimed at restoring cognitive function.