Role of neuronal activity and kinesin on tract tracing by manganese-enhanced MRI (MEMRI)

Role of neuronal activity and kinesin on tract tracing by manganese-enhanced MRI (MEMRI)
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DOI:
10.1016/j.neuroimage.2007.04.053
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发表时间:
2007-01-01
期刊:
影响因子:
5.7
通讯作者:
Jacobs, Russell E.
Jacobs, Russell E.
中科院分区:
医学1区
文献类型:
--
作者:
Bearer, Elaine L.;Falzone, Tomas Luis;Jacobs, Russell E.

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MEMRI提供了通过MRI追踪活体动物神经元回路的令人兴奋的可能性。在这里,我们使用小鼠遗传学的力量和视觉系统的简单性来严格测试影响Mn2+摄取、运输和跨突触追踪的参数。通过测量向眼睛注射Mn2+前后的光响应,我们确定了在11.7T时MR仍可成像的毒性最小的Mn2+的剂量。在遗传性视网膜失明小鼠上,我们发现电活动不是视神经摄取和运输Mn2+所必需的,而是这种示踪剂跨突触传递到这一途径中的远端神经元所必需的。最后,利用Kinesin轻链1基因敲除小鼠,我们发现传统的Kinesin参与了Mn2+在视束中的神经元运输,但不是必需的。这项工作为解释MEMRI获得的大脑回路数据提供了一个分子和生理框架。(C)2007 Elsevier Inc.保留所有权利。
MEMRI offers the exciting possibility of tracing neuronal circuits in living animals by MRI. Here we use the power of mouse genetics and the simplicity of the visual system to test rigorously the parameters affecting Mn2+ uptake, transport and trans-synaptic tracing. By measuring electrical response to light before and after injection of Mn2+ into the eye, we determine the dose of Mn2+ with the least toxicity that can still be imaged by MR at 11.7 T. Using mice with genetic retinal blindness, we discover that electrical activity is not necessary for uptake and transport of Mn2+ in the optic nerve but is required for trans-synaptic transmission of this tracer to distal neurons in this pathway. Finally, using a kinesin light chain 1 knockout mouse, we find that conventional kinesin is a participant but not essential to neuronal transport of Mn2+ in the optic tract. This work provides a molecular and physiological framework for interpreting data acquired by MEMRI of circuitry in the brain. (c) 2007 Elsevier Inc. All rights reserved.