Fast phasic release properties of dopamine studied with a channel biosensor

Few other neurotransmitters are of as intense interest to neuropsychiatry and neurology as dopamine, yet existing techniques to monitor dopamine release leave an important spatiotemporal gap in our understanding. Electrochemistry and fluorescence imaging tools have been developed to fill the gap, bu...

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Published inThe Journal of neuroscience Vol. 34; no. 35; pp. 11792 - 11802
Main Authors Kress, Geraldine J, Shu, Hong-Jin, Yu, Andrew, Taylor, Amanda, Benz, Ann, Harmon, Steve, Mennerick, Steven
Format Journal Article
LanguageEnglish
Published United States Society for Neuroscience 27.08.2014
Subjects
Animals
Biosensing Techniques - methods
Caenorhabditis elegans
Cell Line
Chloride Channels - metabolism
Corpus Striatum - metabolism
Dopamine - secretion
Humans
Ligand-Gated Ion Channels - metabolism
Neurons - secretion
Patch-Clamp Techniques
Rats
Xenopus
striatum
nicotinic
presynaptic
dopamine release
ligand-gated ion channel
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Summary:Few other neurotransmitters are of as intense interest to neuropsychiatry and neurology as dopamine, yet existing techniques to monitor dopamine release leave an important spatiotemporal gap in our understanding. Electrochemistry and fluorescence imaging tools have been developed to fill the gap, but these methods have important limitations. We circumvent these limitations by introducing a dopamine-gated chloride channel into rat dorsal striatal medium spiny neurons, targets of strong dopamine innervation, thereby transforming dopamine from a slow transmitter into a fast transmitter and revealing new opportunities for studying moment-to-moment regulation of dopamine release. We demonstrate pharmacological and biophysical properties of the channel that make it suitable for fast, local dopamine measurements, and we demonstrate for the first time spontaneous and evoked responses to vesicular dopamine release in the dorsal striatum. Evoked dopamine currents were separated into a fast, monosynaptic component and a slower-rising and decaying disynaptic component mediated by nicotinic receptor activation. In summary, LGC-53 represents a dopamine biosensor with properties suitable for temporal separation of distinct dopamine signals in targets of dopamine innervation.
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Author contributions: G.J.K. and S.M. designed research; G.J.K., H.-J.S., A.Y., A.T., A.B., S.H., and S.M. performed research; G.J.K., H.-J.S., A.Y., A.T., and S.M. analyzed data; S.M. wrote the paper.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.2355-14.2014