Yadav-Samudrala Barkha J, Yadav Aryan P, Patel Rahul P, Fitting Sylvia
Department of Psychology and Neuroscience, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Computer Science, The University of North Carolina at Greensboro, Greensboro, NC 27412, USA.
iScience. 2025 Feb 22;28(3):112075. doi: 10.1016/j.isci.2025.112075. eCollection 2025 Mar 21.
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 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.
尽管联合抗逆转录病毒疗法取得了进展，但人类免疫缺陷病毒（HIV）相关神经认知障碍（HAND）仍影响着40%-50%的HIV感染者。虽然神经影像学研究揭示了HIV-1诱导的皮质网络和脑宏观结构改变，但内侧前额叶皮质（mPFC）中的单个神经元在识别记忆过程中如何受到影响仍不清楚。我们在HIV-1转录反式激活因子（Tat）转基因小鼠模型中使用钙成像技术，研究了新物体识别记忆任务期间mPFC神经元的活动。我们的研究结果表明，HIV Tat表达降低了Tat(+)小鼠的整体神经元活动，而不改变激活细胞的数量。此外，根据物体探索情况，Tat(-)和Tat(+)小鼠中不同的神经元亚群会被上调和下调。重要的是，HIV Tat表达破坏了由熟悉度驱动的mPFC活动增加。这些发现增进了我们对HAND的理解，并可能为未来旨在恢复认知功能的药理学策略提供信息。
