Davidson Andrew M, Mejía-Gómez Hernán, Wooten Bryn M, Marqués Sharai, Jacobowitz Michael, Ugidos Irene F, Mostany Ricardo
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA, USA.
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA.
Geroscience. 2024 Sep 30. doi: 10.1007/s11357-024-01350-6.
Changes to neuronal connectivity are believed to be a key factor in cognitive impairments associated with normal aging. Because of its effect on activities of daily living, deficient motor control is a critical type of cognitive decline to understand. Diminished inhibitory networks in the cortex are implicated in such motor control deficits, pointing to the connectivity of inhibitory cortical interneurons as an important area for study. Here, we used chronic two-photon microscopy to track the structural plasticity of en passant boutons (EPBs) of parvalbumin-positive interneurons in the mouse motor cortex in the first longitudinal, in vivo study of inhibitory interneuron synapses in the context of aging. Young (3-5 months) and aged (23-28 months) mice underwent training on the accelerating rotarod to evoke motor learning-induced structural plasticity. Our analysis reveals that, in comparison with axons from young mice, those from aged mice have fewer EPBs at baseline that also tend to be larger in size. Aged axons also express learning-related structural plasticity-like new bouton stabilization and bouton enlargement-that is less persistent than that of young axons. This study reveals striking baseline differences in young and aged axon morphology as well as differences in the deployment of learning-related structural plasticity across axons.
神经元连接的变化被认为是与正常衰老相关的认知障碍的关键因素。由于其对日常生活活动的影响，运动控制不足是一种需要理解的关键认知衰退类型。皮层中抑制性网络的减弱与这种运动控制缺陷有关，这表明抑制性皮层中间神经元的连接性是一个重要的研究领域。在此，我们在衰老背景下对抑制性中间神经元突触进行了首次纵向体内研究，使用慢性双光子显微镜追踪小鼠运动皮层中小清蛋白阳性中间神经元的旁支终扣（EPB）的结构可塑性。年轻（3 - 5个月）和老年（23 - 28个月）小鼠在加速旋转杆上接受训练，以诱发运动学习诱导的结构可塑性。我们的分析表明，与年轻小鼠的轴突相比，老年小鼠的轴突在基线时的EPB较少，且往往尺寸更大。老年轴突也表现出与学习相关的结构可塑性，如新生终扣稳定和终扣增大，但不如年轻轴突持久。这项研究揭示了年轻和老年轴突形态在基线时的显著差异，以及轴突间与学习相关的结构可塑性表现的差异。
