Hai Aviad, Cai Lili X, Lee Taekwan, Lelyveld Victor S, Jasanoff Alan
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Nuclear Science & Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Neuron. 2016 Nov 23;92(4):754-765. doi: 10.1016/j.neuron.2016.09.048. Epub 2016 Oct 20.
Reuptake of neurotransmitters from the brain interstitium shapes chemical signaling processes and is disrupted in several pathologies. Serotonin reuptake in particular is important for mood regulation and is inhibited by first-line drugs for treatment of depression. Here we introduce a molecular-level fMRI technique for micron-scale mapping of serotonin transport in live animals. Intracranial injection of an MRI-detectable serotonin sensor complexed with serotonin, together with serial imaging and compartmental analysis, permits neurotransmitter transport to be quantified as serotonin dissociates from the probe. Application of this strategy to much of the striatum and surrounding areas reveals widespread nonsaturating serotonin removal with maximal rates in the lateral septum. The serotonin reuptake inhibitor fluoxetine selectively suppresses serotonin removal in septal subregions, whereas both fluoxetine and a dopamine transporter blocker depress reuptake in striatum. These results highlight promiscuous pharmacological influences on the serotonergic system and demonstrate the utility of molecular fMRI for characterization of neurochemical dynamics.
神经递质从脑间质的再摄取塑造了化学信号传导过程，并且在多种病理状态下会受到破坏。特别是血清素再摄取对情绪调节很重要，并且会被治疗抑郁症的一线药物所抑制。在此，我们介绍一种用于在活体动物中对血清素转运进行微米级映射的分子水平功能磁共振成像（fMRI）技术。向颅内注射与血清素复合的可被MRI检测到的血清素传感器，结合连续成像和隔室分析，随着血清素与探针解离，可对神经递质转运进行量化。将该策略应用于大部分纹状体及周边区域，结果显示血清素广泛以非饱和方式被清除，在外侧隔区清除率最高。血清素再摄取抑制剂氟西汀选择性地抑制隔区亚区域的血清素清除，而氟西汀和多巴胺转运体阻滞剂都会抑制纹状体中的再摄取。这些结果突出了对血清素能系统的混杂药理学影响，并证明了分子fMRI在表征神经化学动力学方面的实用性。
