Manno Francis A M, An Ziqi, Kumar Rachit, Su Junfeng, Liu Jiaming, Wu Ed X, He Jufang, Feng Yanqiu, Lau Condon
Department of Physics, City University of Hong Kong, Hong Kong SAR, China; Center for Imaging Science, Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
School of Biomedical Engineering, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Medical Image Processing & Guangdong Province Engineering Laboratory for Medical Imaging and Diagnostic Technology, Southern Medical University, Guangzhou, China; Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence & Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, China.
Neuroimage. 2022 May 15;252:119016. doi: 10.1016/j.neuroimage.2022.119016. Epub 2022 Feb 18.
Environmental enrichment induces widespread neuronal changes, but the initiation of the cascade is unknown. We ascertained the critical period of divergence between environmental enriched (EE) and standard environment (SE) mice using continuous infrared (IR) videography, functional magnetic resonance imaging (fMRI), and neuron level calcium imaging. Naïve adult male mice (n = 285, C57BL/6J, postnatal day 60) were divided into SE and EE groups. We assessed the linear time-series of motion activity using a novel structural break test which examined the dataset for change in circadian and day-by-day motion activity. fMRI was used to map brain-wide response using a functional connectome analysis pipeline. Awake calcium imaging was performed on the dorsal CA1 pyramidal layer. We found the preeminent behavioral feature in EE was a forward shift in the circadian rhythm, prolongation of activity in the dark photoperiod, and overall decreased motion activity. The crepuscular period of dusk was seen as the critical period of divergence between EE and SE mice. The functional processes at dusk in EE included increased functional connectivity in the visual cortex, motor cortex, retrosplenial granular cortex, and cingulate cortex using seed-based analysis. Network based statistics found a modulated functional connectome in EE concentrated in two hubs: the hippocampal formation and isocortical network. These hubs experienced a higher node degree and significant enhanced edge connectivity. Calcium imaging revealed increased spikes per second and maximum firing rate in the dorsal CA1 pyramidal layer, in addition to location (anterior-posterior and medial-lateral) effect size differences between EE and SE. The emergence of functional-neuronal changes due to enrichment consisted of enhanced hippocampal-isocortex functional connectivity and CA1 neuronal increased spiking linked to a circadian shift during the dusk period. Future studies should explore the molecular consequences of enrichment inducing shifts in the circadian period.
环境富集会引发广泛的神经元变化，但该级联反应的起始因素尚不清楚。我们使用连续红外（IR）摄像、功能磁共振成像（fMRI）和神经元水平钙成像，确定了环境富集（EE）小鼠和标准环境（SE）小鼠之间出现差异的关键时期。将新生成年雄性小鼠（n = 285，C57BL/6J，出生后第60天）分为SE组和EE组。我们使用一种新颖的结构断点测试评估运动活动的线性时间序列，该测试检查数据集以寻找昼夜节律和每日运动活动的变化。fMRI用于通过功能连接组分析流程绘制全脑反应图谱。在背侧CA1锥体层进行清醒钙成像。我们发现EE小鼠最突出的行为特征是昼夜节律向前偏移、暗期活动延长以及整体运动活动减少。黄昏的黄昏期被视为EE小鼠和SE小鼠之间出现差异的关键时期。EE小鼠在黄昏时的功能过程包括使用基于种子的分析方法，视觉皮层、运动皮层、 retrosplenial颗粒皮层和扣带皮层的功能连接增加。基于网络的统计发现，EE小鼠中一个经过调制的功能连接组集中在两个枢纽：海马结构和同皮质网络。这些枢纽具有更高的节点度和显著增强的边缘连接性。钙成像显示，除了EE小鼠和SE小鼠之间在位置（前后和内外侧）效应大小上存在差异外，背侧CA1锥体层每秒的尖峰数和最大放电率也有所增加。由于富集导致的功能 - 神经元变化的出现包括增强的海马 - 同皮质功能连接以及与黄昏期间昼夜节律变化相关的CA1神经元尖峰增加。未来的研究应探索富集诱导昼夜节律变化的分子后果。
