Fast phasic release properties of dopamine studied with a channel biosensor

Geraldine J. Kress, Hong Jin Shu, Andrew Yu, Amanda Taylor, Ann Benz, Steve Harmon, Steven Mennerick

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)11792-11802
Number of pages11
JournalJournal of Neuroscience
Volume34
Issue number35
DOIs
StatePublished - Aug 27 2014

Keywords

  • Dopamine release
  • Ligand-gated ion channel
  • Nicotinic
  • Presynaptic
  • Striatum

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