In vivo imaging of neuromodulatory synaptic transmission using PET: A review of relevant neurophysiology
In vivo imaging of neuromodulatory synaptic transmission using PET: A review of relevant neurophysiology
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DOI：
10.1002/hbm.460030104
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发表时间：
1995-01-01
影响因子：
4.8
通讯作者：
Fischman, AJ
中科院分区：
文献类型：
--
作者：
Fisher, RE;Morris, ED;Fischman, AJ
正电子发射断层扫描（PET）成像研究的最新数据表明，在人体内研究突触传递的可能性。该方法将需要综合两种已建立的技术：脑激活研究（通常通过测量局部脑血流量或代谢进行）和神经递质受体成像（使用与特定神经受体结合的放射性标记配体）。通过比较受试者在休息时和执行激活任务时的神经受体结合，可以确定特定的神经递质是否参与任务的执行。其基本原理是内源性神经递质与注射的放射性配体竞争相同的受体，从而抑制配体结合。这种效应在激活过程中会更加明显，因为突触中递质浓度升高。因此，特定神经递质的激活将被检测为放射性配体的特异性结合的减少。在本文中，我们回顾神经生理学和生物化学文献，估计内源性神经递质浓度的变化，预计将发生在一个激活任务，使用多巴胺系统作为一个例子。我们计算出平均突触多巴胺浓度约为100 nM，并且在激活期间约加倍。这一点，沿着考虑放射性配体的浓度以及配体和多巴胺对多巴胺受体的亲和力，表明特定神经递质系统的生理激活可能可以用PET检测到。(C)1995 Wiley-Liss，Inc.
Recent data from positron emission tomography (PET) imaging studies suggest the possibility of studying synaptic transmission in vivo in humans. The approach will require a synthesis of two established techniques: brain activation studies (conventionally performed by measuring regional cerebral blood flow or metabolism) and neurotransmitter receptor imaging (using radiolabelled ligands that bind to specific neuroreceptors). By comparing neuroreceptor binding in subjects at rest and while performing an activation task, it may be possible to determine whether a particular neurotransmitter is involved in performance of the task. The underlying principle is that endogenous neurotransmitter competes with the injected radioligand for the same receptors, thereby inhibiting ligand binding. This effect will be even more pronounced during activation, as the synaptic concentration of transmitter rises. Thus, activation of a specific neurotransmitter will be detected as a decrease in specific binding of the radioligand. In this paper we review neurophysiological and biochemical literature to estimate the endogenous neurotransmitter concentration changes that will be expected to occur during an activation task, using the dopamine system as an example. We calculate that the average synaptic dopamine concentration is approximate to 100 nM and that it approximately doubles during activation. This, along with consideration of the concentration of radioligand and affinities of the ligand and dopamine for dopamine receptors, suggests that physiological activation of a specific neurotransmitter system is likely to be detectable with PET. (C) 1995 Wiley-Liss, Inc.