title: Fast phasic release properties of dopamine studied with a channel biosensor.
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.
authors.affiliation: Departments of Psychiatry and.
authors.forename: Geraldine J
authors.initials: GJ
authors.lastname: Kress
authors.affiliation: Departments of Psychiatry and.
authors.forename: Hong-Jin
authors.initials: HJ
authors.lastname: Shu
authors.affiliation: Departments of Psychiatry and.
authors.forename: Andrew
authors.initials: A
authors.lastname: Yu
authors.affiliation: Departments of Psychiatry and.
authors.forename: Amanda
authors.initials: A
authors.lastname: Taylor
authors.affiliation: Departments of Psychiatry and.
authors.forename: Ann
authors.initials: A
authors.lastname: Benz
authors.affiliation: Anatomy and Neurobiology and.
authors.forename: Steve
authors.initials: S
authors.lastname: Harmon
authors.affiliation: Departments of Psychiatry and Anatomy and Neurobiology and Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, Missouri 63110 menneris@wustl.edu.
authors.forename: Steven
authors.initials: S
authors.lastname: Mennerick
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D017173:Caenorhabditis elegans; D002460:Cell Line; D018118:Chloride Channels / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D058446:Ligand-Gated Ion Channels / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D014981:Xenopus
chemical_list: D018118:Chloride Channels; D058446:Ligand-Gated Ion Channels; D004298:Dopamine
keywords: dopamine release; ligand-gated ion channel; nicotinic; presynaptic; striatum