title: Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission.
abstract: The mesolimbic dopamine system is centrally involved in reward and goal-directed behavior, and it has been implicated in multiple psychiatric disorders. Understanding the mechanism by which dopamine participates in these activities requires comprehension of the dynamics of dopamine release. Here we report dissociable regulation of dopamine neuron discharge by two separate afferent systems in rats; inhibition of pallidal afferents selectively increased the population activity of dopamine neurons, whereas activation of pedunculopontine inputs increased burst firing. Only the increase in population activity increased ventral striatal dopamine efflux. After blockade of dopamine reuptake, however, enhanced bursting increased dopamine efflux three times more than did enhanced population activity. These results provide insight into multiple regulatory systems that modulate dopamine system function: burst firing induces massive synaptic dopamine release, which is rapidly removed by reuptake before escaping the synaptic cleft, whereas increased population activity modulates tonic extrasynaptic dopamine levels that are less influenced by reuptake.
authors.affiliation: Department of Neuroscienc, University of Pittsburgh, 446 Crawford Hall, Pittsburgh, Pennsylvania 15260, USA. floresco@psych.ubc.ca
authors.forename: Stan B
authors.initials: SB
authors.lastname: Floresco
authors.forename: Anthony R
authors.initials: AR
authors.lastname: West
authors.forename: Brian
authors.initials: B
authors.lastname: Ash
authors.forename: Holly
authors.initials: H
authors.lastname: Moore
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Grace
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
chemical_list: D018756:GABA Antagonists; D004298:Dopamine