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.尽管联合抗逆转录病毒疗法取得了进展，但HIV相关神经认知障碍（HIV-associated neurocognitive disorders, HAND）仍会影响40%~50%的艾滋病病毒感染者。尽管神经影像学研究已揭示HIV-1诱导的皮层网络与大脑宏观结构改变，但内侧前额叶皮层（medial prefrontal cortex, mPFC）内的单个神经元在识别记忆过程中如何受影响仍不明确。本研究通过在HIV-1 Tat转基因小鼠模型中采用在体钙成像技术，在新物体识别记忆任务中检测了内侧前额叶皮层的神经元活动。研究结果显示，HIV Tat表达会降低Tat(+)小鼠的整体神经元活动，但不会改变激活细胞的数量。此外，在Tat(–)和Tat(+)小鼠中，不同的神经元亚群会根据物体探索行为分别出现上调与下调调节。重要的是，熟悉性驱动的内侧前额叶皮层活动增强被HIV Tat表达所破坏。本研究结果加深了我们对HAND相关认知缺陷的理解，或可为未来恢复认知功能的药理学策略提供参考。