Toward Serotonin Fluorescent False Neurotransmitters: Development of Fluorescent Dual Serotonin and Vesicular Monoamine Transporter Substrates for Visualizing Serotonin Neurons

Henke, Adam; Kovalyova, Yekaterina; Dunn, Matthew R.; Dreier, Dominik; Gubernator, Niko G.; Dincheva, Iva; Hwu, Christopher; Šebej, Peter; Ansorge, Mark S.; Sulzer, David; Sameš, Dalibor

doi:10.1021/acschemneuro.7b00320

Cited by 35 publications

(34 citation statements)

References 51 publications

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“…Upon potassium and electrically induced stimulation of FFN-labeled tissue, FFN511 and other similar constructs (FFN200, FFN202, FFN102) have enabled visualization of dopamine vesicular exocytosis with synapse-scale spatial resolution 38–41 . Using a similar approach, an optical tracer for serotonin (FFN 246) has shown modest success as well 42 …”

Section: Synthetic Probesmentioning

confidence: 99%

Review Article: Tools and trends for probing brain neurochemistry

Beyene

Yang

Landry

2019

Journal of Vacuum Science &Amp; Technology A: Vacuum, Surfaces, and Films

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The brain is composed of complex neuronal networks that interact on spatial and temporal scales that span several orders of magnitude. Uncovering how this circuitry gives rise to multifaceted phenomena such as perception, memory, and behavior remains one of the grand challenges in science today. A wide range of investigative methods have been developed to delve deeper into the inner workings of the brain, spanning the realms of molecular biology, genetics, chemistry, optics, and engineering, thereby forming a nexus of discovery that has accelerated our understanding of the brain. Whereas neuronal electrical excitability is a hallmark property of neurons, chemical signaling between neurons—mediated by hundreds of neurotransmitters, neuromodulators, hormones, and other signaling molecules—is equally important, but far more elusive in its regulation of brain function for motor control, learning, and behavior. To date, the brain's neurochemical state has been interrogated using classical tools borrowed from analytical chemistry, such as liquid chromatography and amperometry, and more recently, newly developed fluorescent sensors. Here, the authors review advances in the development of functional fluorescent probes that are beginning to expand their understanding of the neurochemical basis of brain function alongside device-based analytical tools that have already made extensive contributions to the field. The emphasis herein is on the paradigms of probe and device development, which follow certain design principles unique to the interrogation of brain chemistry.

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Section: Synthetic Probesmentioning

confidence: 99%

Review Article: Tools and trends for probing brain neurochemistry

Beyene

Yang

Landry

2019

Journal of Vacuum Science &Amp; Technology A: Vacuum, Surfaces, and Films

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“…However, previous methods suffer from limited spatial resolution, and microdialysis sampling occurs on the order of minutes, which precludes assaying fast 5-HT modulatory transients in the brain. While a few optical probes for 5-HT of varying selectivity have been developed, to date, none have been implemented for monitoring 5-HT modulation on spatiotemporal scales relevant to monitoring endogenous 5-HT kinetics (16)(17)(18)(19)(20)(21). This lack of tools to probe the dynamics of neuromodulators such as 5-HT stems from the difficulty in developing synthetic optical probes for extracellular analytes.…”

Section: Introductionmentioning

confidence: 99%

High-throughput evolution of near-infrared serotonin nanosensors

et al. 2019

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Imaging neuromodulation with synthetic probes is an emerging technology for studying neurotransmission. However, most synthetic probes are developed through conjugation of fluorescent signal transducers to preexisting recognition moieties such as antibodies or receptors. We introduce a generic platform to evolve synthetic molecular recognition on the surface of near-infrared fluorescent single-wall carbon nanotube (SWCNT) signal transducers. We demonstrate evolution of molecular recognition toward neuromodulator serotonin generated from large libraries of ~6.9 × 1010 unique ssDNA sequences conjugated to SWCNTs. This probe is reversible and produces a ~200% fluorescence enhancement upon exposure to serotonin with a Kd = 6.3 μM, and shows selective responsivity over serotonin analogs, metabolites, and receptor-targeting drugs. Furthermore, this probe remains responsive and reversible upon repeat exposure to exogenous serotonin in the extracellular space of acute brain slices. Our results suggest that evolution of nanosensors could be generically implemented to develop other neuromodulator probes with synthetic molecular recognition.

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“…The small association constant ( K ∼ 10 2 to 10 4 M –1 ) of iminium and boronic acid catechol ester may also limit its application to samples with a high catecholamine concentration. Other bioanalytical methods such as liquid chromatography,25–27 electrochemical methods28,29 and the use of fluorescent false neurotransmitters30–34 are either not applicable in living cells or only indirectly studying neuronal activity.…”

Section: Introductionmentioning

confidence: 99%