Genetically encoded neurotransmitter sensors will shed light on neuronal communication.
Neurotransmitters can be considered the vocabulary of the neuronal language. Neurons release neurotransmitters at the synapse to communicate with their receiving partners. The effects on the postsynaptic partner can be either excitatory or inhibitory. In addition, neurons can release neurotransmitters that diffuse and modulate populations of neurons. The neurotransmitter vocabulary is diverse and includes molecules such as amino acids (e.g., glutamate), monoamines (e.g., dopamine), peptides and others. Genetically encoded sensors help to decipher the communications between neurons, both at the circuit level and at a more detailed mechanistic level.
Several neurotransmitter sensors have been developed. The glutamate sensor iGluSnFR has been popular for studies of the predominant neurotransmitter in the vertebrate brain (Nat. Methods 10, 162–170; 2013), and improved versions have recently been reported (Nat. Methods 15, 936–939; 2018). Genetically encoded sensors for dopamine (GRABDA, dLight1) and acetylcholine (GACh) are now available as well (Cell 174, 481–496, 2018; Science 360, 1420, 2018; Nat. Biotechnol. 36, 726–737, 2018).
The glutamate sensors are based on a bacterial protein, and the engineering strategy is not easily generalizable. In contrast, the dopamine and acetylcholine sensors are based on their cognate endogenous receptors—G-protein-coupled receptors—fused to a fluorescent protein. As many neurotransmitters signal through G-protein-coupled receptors, a similar design principle can potentially be used to generate sensors for other neurotransmitters, such as the monoamines norepinephrine and serotonin and the endorphin peptide family.
Expanding the palette of neurotransmitter sensors should help scientists better understand the intricate interplay among excitatory, inhibitory and modulatory neurotransmission. These sensors will provide a glimpse at the spatial and temporal relationships of such signaling events in neuronal circuits.
We look forward to the development of additional neurotransmitter sensors and their application in deciphering the language of the brain.
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