Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, 60612, United States.
Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, 60612, United States.
Neurosci Lett. 2019 Aug 24;708:134341. doi: 10.1016/j.neulet.2019.134341. Epub 2019 Jun 27.
The medial prefrontal cortex (mPFC) is a key regulator of neurocognition. The glutamatergic pyramidal neurons are the predominant component of neurons in the mPFC. Aging and HIV profoundly alter the structure and function of mPFC pyramidal neurons, including, but are not limited to, dysregulation of NMDA receptors and voltage-gated calcium channels. Here we assessed the impact of aging and in vivo HIV exposure on the functional activity (firing) of mPFC pyramidal neurons mediated by voltage-gated K (K) channels and inwardly-rectifying K (K) channels using patch-clamp recording in rat brain slices ex vivo. We found that aging and HIV significantly affect firing in different manners by altering the activity of K and likely K channels, associated with changes in membrane properties and the mRNA levels of specific K channels. Evoked firing was significantly decreased in mPFC neurons of older (12 month, 12 m) rats compared to younger (6/7 week, 6/7wk) rats, regardless of HIV status. In contrast, firing was significantly increased in neurons from Tg rats compared to non-Tg rats, regardless of age. Aging/HIV-induced alterations in firing were mediated by dysfunctional K channels and K channels, which exhibit significant changes in their activity and/or expression induced by aging and HIV exposure in vivo. Collectively, these novel findings demonstrate that aging is associated with a significant decline of mPFC neuronal activity; while long-term HIV exposure in vivo could drive mPFC neurons from over-activation to loss of firing, which could ultimately exacerbate the decline of mPFC neuronal activity.
内侧前额叶皮层（mPFC）是神经认知的关键调节者。谷氨酸能锥体神经元是 mPFC 神经元的主要组成部分。衰老和 HIV 会深刻改变 mPFC 锥体神经元的结构和功能，包括但不限于 NMDA 受体和电压门控钙通道的失调。在这里，我们使用离体大鼠脑片的膜片钳记录评估了衰老和体内 HIV 暴露对 mPFC 锥体神经元电压门控 K（K）通道和内向整流 K（K）通道介导的功能活动（放电）的影响。我们发现，衰老和 HIV 通过改变 K 和可能的 K 通道的活性以不同的方式显著影响放电，这与膜特性的变化和特定 K 通道的 mRNA 水平有关。与年轻（6/7 周，6/7wk）大鼠相比，老年（12 个月，12m）大鼠的 mPFC 神经元的诱发放电显著减少，而与 HIV 状态无关。相比之下，无论年龄大小，Tg 大鼠的神经元放电均显著增加。mPFC 神经元放电的衰老/HIV 诱导改变是由功能失调的 K 通道和 K 通道介导的，这些通道的活性和/或表达在体内衰老和 HIV 暴露的诱导下发生显著变化。总的来说，这些新发现表明，衰老与 mPFC 神经元活动的显著下降有关；而体内长期 HIV 暴露可能会导致 mPFC 神经元从过度兴奋到放电丧失，这最终可能会加剧 mPFC 神经元活动的下降。
