Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore.
Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore; Clinical Imaging Research Centre, National University of Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Neuroimage. 2014 Feb 1;86:417-24. doi: 10.1016/j.neuroimage.2013.10.025. Epub 2013 Oct 22.
Resting-state functional connectivity, manifested as spontaneous synchronous activity in the brain, has been detected by functional MRI (fMRI) across species such as humans, monkeys, and rats. Yet, most networks, especially the classical bilateral connectivity between hemispheres, have not been reliably found in the mouse brain. This could be due to anesthetic effects on neural activity and difficulty in maintaining proper physiology and neurovascular coupling in anesthetized mouse. For example, α2 adrenoceptor agonist, medetomidine, is a sedative for longitudinal mouse fMRI. However, the higher dosage needed compared to rats may suppress the functional synchrony and lead to unilateral connectivity. In this study, we investigated the influence of medetomidine dosage on neural activation and resting-state networks in mouse brain. We show that mouse can be stabilized with dosage as low as 0.1mg/kg/h. The stimulation-induced somatosensory activation was unchanged when medetomidine was increased from 0.1 to 6 and 10 folds. Especially, robust bilateral connectivity can be observed in the primary, secondary somatosensory and visual cortices, as well as the hippocampus, caudate putamen, and thalamus at low dose of medetomidine. Significant suppression of inter-hemispheric correlation was seen in the thalamus, where the receptor density is high, under 0.6mg/kg/h, and in all regions except the caudate, where the receptor density is low, under 1.0mg/kg/h. Furthermore, in mice whose activation was weaker or took longer time to detect, the bilateral connectivity was lower. This demonstrates that, with proper sedation and conservation of neurovascular coupling, similar bilateral networks like other species can be detected in the mouse brain.
静息态功能连接，表现为大脑中的自发性同步活动，已经通过功能磁共振成像 (fMRI) 在人类、猴子和老鼠等物种中被检测到。然而，大多数网络，特别是经典的大脑两半球之间的双侧连接，在老鼠大脑中并没有被可靠地发现。这可能是由于麻醉对神经活动的影响以及在麻醉老鼠中难以维持适当的生理学和神经血管耦联。例如，α2 肾上腺素能受体激动剂，美托咪定，是纵向老鼠 fMRI 的镇静剂。然而，与大鼠相比，所需的更高剂量可能会抑制功能同步性并导致单侧连接。在这项研究中，我们研究了美托咪定剂量对老鼠大脑神经激活和静息态网络的影响。我们表明，老鼠可以用低至 0.1mg/kg/h 的剂量稳定下来。当美托咪定增加到 0.1 到 6 和 10 倍时，刺激诱导的感觉激活没有变化。特别是，在低剂量的美托咪定下，可以观察到初级、次级感觉和视觉皮层以及海马体、尾状核、苍白球和丘脑的强烈双侧连接。在丘脑（其受体密度较高）下 0.6mg/kg/h 和除尾状核（其受体密度较低）以外的所有区域下 1.0mg/kg/h 下，观察到双侧相关性的显著抑制。此外，在激活较弱或需要更长时间才能检测到的老鼠中，双侧连接较低。这表明，通过适当的镇静和神经血管耦联的保护，可以在老鼠大脑中检测到类似于其他物种的相似双侧网络。
