Chemical Compounds That Transmit Neural Signals From One Neuron

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3.3.1 Neurotransmitter indicators
Neurotransmitters are endogenous chemical compounds that transmit neural signals from one neuron to another. Many neurotransmitters are amino acids, such as glutamate, glycine and GABA, or biogenic amines, such as dopamine and serotonin, or even peptides and proteins, such as somatostatin and substance P {Snyder 1979}. Binding of neurotransmitters may either inhibit or excite the postsynaptic neurons. Among the numerous neurotransmitters, glutamate is the major excitatory amino acid neurotransmitter in mammalian neural systems {Cotman 1986}. The first genetically encoded neurotransmitter for glutamate was reported in 2005 {Okumoto, 2005 #292}. Upon binding to glutamate, the indicator converts the
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IGluSnFR was engineered in vitro for maximized fluorescence response, and it could robustly detect glutamate release events with sufficient SNR and kinetics for in vivo imaging in worms, zebrafish, and mice {Marvin, 2013 #864}. Notably, bacteria express a variety of periplasmic binding proteins including ones for GABA, acetylcholine, glycine and other small molecules that serve as neurotransmitter in the brain . A design principle similar to that used for iGluSnFR may one day produce a series of genetically encoded indicators for probing various neurotransmitters with spine-sized spatial resolution.
Instead of probing the neurotransmitters directly, one could probe the neurotransmitter binding events by coupling it to a different optical readout using a multi-component system. Nguyen et al. described a multi-component system, called cell-based neurotransmitter fluorescent engineered reporters (CNiFERs), to monitor in situ neurotransmitter receptor activation {Nguyen, 2010 #921}. CNiFERs are engineered cultured cells that stably express an M1 acetylcholine receptor and the GECI TN-XXL. The system utilizes the GPCR cascade to convert receptor activity into a rise in cytosolic Ca2+ which is reported by TN-XXL. Nguyen et al. injected CNiFERs in the frontal cortex of the adult rat and used CNiFERs to probe the change of cholinergic signaling induced by an atypical neuroleptic drug {Nguyen, 2010 #921}. Substitution of the M1 receptor with other Cys-loop receptors produced
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