Age- and sex-dependent alterations in primary somatosensory cortex neuronal calcium network dynamics during locomotion.
Age- and sex-dependent alterations in primary somatosensory cortex neuronal calcium network dynamics during locomotion.
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DOI：
10.1111/acel.13898
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发表时间：
2023-08
期刊：
影响因子：
7.8
通讯作者：
Thibault, Olivier
中科院分区：
文献类型：
--
作者：
Case, Sami L.;Lin, Ruei-Lung;Thibault, Olivier
关键词：
在过去的30年里，钙（Ca2+）脑老化假说提供了明确的证据，表明海马神经元Ca2+失调是衰老的关键生物标志物。年龄依赖的Ca2+介导的内在兴奋性、突触可塑性和活动的变化有助于确定一些参与记忆和认知衰退的机制，这些机制主要是在单细胞水平和切片制备中完成的。最近，我们的实验室在麻醉动物的皮质中发现了年龄和Ca2+相关的神经网络失调。尽管如此，仍需要在清醒的动物中进行调查，以测试Ca2+脑衰老假说的普遍性。在这里，我们对行走的小鼠进行了双光子成像，在行走和休息时对初级体感觉皮层（S1）中的GCaMP8f进行了成像。我们研究了C56BL/6J小鼠神经元网络中衰老和性别相关的变化。成像后，对步态行为进行表征，以测试运动稳定性的变化。在行走过程中，在年轻成年小鼠和老年小鼠中，网络连通性和同步性都有所增加。仅在行走的老年男性中观察到同步性的年龄依赖性增加。此外，与男性相比，女性的活跃神经元数量、Ca2+瞬态和神经元活动都有所增加，尤其是在行走时。这些结果表明S1 Ca2+动力学和网络同步性可能是运动稳定性的贡献者。我们相信这项研究提高了人们对S1神经元网络中年龄和性别依赖性改变的认识，这可能是随着年龄增长而增加跌倒的原因。在这里，我们对不同年龄和性别的行走小鼠进行了自发双光子成像，对初级体感皮层（S1）中的GCaMP8f进行了成像，并对神经元网络进行了表征。在行走过程中，在年轻成年小鼠和老年小鼠中，网络连通性和同步性都有所增加。仅在行走的老年男性中观察到同步性的年龄依赖性增加。此外，与男性相比，女性的活跃神经元数量、Ca2+瞬态和神经元活动都有所增加，尤其是在行走时。
Over the past 30 years, the calcium (Ca2+) hypothesis of brain aging has provided clear evidence that hippocampal neuronal Ca2+ dysregulation is a key biomarker of aging. Age‐dependent Ca2+‐mediated changes in intrinsic excitability, synaptic plasticity, and activity have helped identify some of the mechanisms engaged in memory and cognitive decline based on work done mostly at the single‐cell level and in the slice preparation. Recently, our lab identified age‐ and Ca2+‐related neuronal network dysregulation in the cortex of the anesthetized animal. Still, investigations in the awake animal are needed to test the generalizability of the Ca2+ hypothesis of brain aging. Here, we used in vigilo two‐photon imaging in ambulating mice, to image GCaMP8f in the primary somatosensory cortex (S1), during ambulation and at rest. We investigated aging‐ and sex‐related changes in neuronal networks in the C56BL/6J mouse. Following imaging, gait behavior was characterized to test for changes in locomotor stability. During ambulation, in both young adult and aged mice, an increase in network connectivity and synchronicity was noted. An age‐dependent increase in synchronicity was seen in ambulating aged males only. Additionally, females displayed increases in the number of active neurons, Ca2+ transients, and neuronal activity compared to males, particularly during ambulation. These results suggest S1 Ca2+ dynamics and network synchronicity are likely contributors of locomotor stability. We believe this work raises awareness of age‐ and sex‐dependent alterations in S1 neuronal networks, perhaps underlying the increase in falls with age. Here, we used in vigilo two‐photon imaging in ambulating mice across age and sex, to image GCaMP8f in the primary somatosensory cortex (S1) and characterize neuronal networks. During ambulation, in both young adult and aged mice, an increase in network connectivity and synchronicity was noted. An age‐dependent increase in synchronicity was seen in ambulating aged males only. Additionally, females displayed increases in the number of active neurons, Ca2+ transients, and neuronal activity compared to males, particularly during ambulation.
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