The basal ganglia are important modulators of the cognitive and motor benefits of exercise. However, the neural networks underlying these benefits remain poorly understood. Our study systematically analyzed exercise-associated changes in metabolic connectivity in the cortico-basal ganglia-thalamic network during the performance of a new motor task, with regions-of-interest defined based on mesoscopic domains recently defined in the mouse brain structural connectome. Mice were trained on a motorized treadmill for six weeks or remained sedentary (control), thereafter undergoing [¹⁴C]-2-deoxyglucose metabolic brain mapping during wheel walking. Regional cerebral glucose uptake (rCGU) was analyzed in 3-dimensional brains reconstructed from autoradiographic brain sections using statistical parametric mapping. Metabolic connectivity was assessed by calculating inter-regional correlation of rCGU cross-sectionally across subjects within a group. Compared to controls, exercised animals showed broad decreases in rCGU in motor areas, but increases in limbic areas, as well as the visual and association cortices. In addition, exercised animals showed (i) increased positive metabolic connectivity within and between the motor cortex and caudoputamen (CP), (ii) newly emerged negative connectivity of the substantia nigra pars reticulata with the globus pallidus externus, and CP, and (iii) reduced connectivity of the prefrontal cortex (PFC). Increased metabolic connectivity in the motor circuit in the absence of increases in rCGU strongly suggests greater network efficiency, which is also supported by the reduced involvement of PFC-mediated cognitive control during the performance of a new motor task. Our study delineates exercise-associated changes in functional circuitry at the subregional level and provides a framework for understanding the effects of exercise on functions of the cortico-basal ganglia-thalamic network.

基底神经节是运动认知和运动益处的重要调节器。然而，这些好处背后的神经网络仍然知之甚少。我们的研究系统地分析了在执行新的运动任务期间皮质-基底节-丘脑网络中与运动相关的代谢连接的变化，并根据最近在小鼠大脑结构连接组中定义的介观域来定义感兴趣的区域。小鼠在电动跑步机上训练六周或保持静坐（对照），然后在轮行走期间进行[ ¹⁴ C]-2-脱氧葡萄糖代谢脑图谱分析。使用统计参数映射从放射自显影脑切片重建的 3 维大脑中分析区域脑葡萄糖摄取 (rCGU)。通过计算组内受试者横断面 rCGU 的区域间相关性来评估代谢连接性。与对照组相比，运动动物的运动区域 rCGU 大幅下降，但边缘区域以及视觉和关联皮层的 rCGU 增加。此外，运动动物表现出（i）运动皮层和尾壳核（CP）内部和之间的正代谢连接增加，（ii）黑质网状部与苍白球外部和CP之间新出现的负连接，以及（iii） ）前额皮质（PFC）的连接性降低。在 rCGU 不增加的情况下，运动回路中代谢连接的增加强烈表明网络效率更高，这也得到了执行新运动任务期间 PFC 介导的认知控制参与减少的支持。我们的研究描绘了次区域水平上与运动相关的功能回路变化，并为理解运动对皮质基底节丘脑网络功能的影响提供了一个框架。