title: Phasic dopaminergic activity exerts fast control of cholinergic interneuron firing via sequential NMDA, D2, and D1 receptor activation.
abstract: Phasic increases in dopamine (DA) are involved in the detection and selection of relevant sensory stimuli. The DAergic and cholinergic system dynamically interact to gate and potentiate sensory inputs to striatum. Striatal cholinergic interneurons (CINs) respond to relevant sensory stimuli with an initial burst, a firing pause, or a late burst, or a combination of these three components. CIN responses coincide with phasic firing of DAergic neurons in vivo. In particular, the late burst of CINs codes for the anticipated reward. To examine whether DAergic midbrain afferents can evoke the different CIN responses, we recorded from adult olfactory tubercle slices in the mouse ventral striatum. Olfactory inputs to striatal projection neurons were gated by the cholinergic tone. Phasic optogenetic activation of DAergic terminals evoked combinations of initial bursts, pauses, and late bursts in subsets of CINs by distinct receptor pathways. Glutamate release from midbrain afferents evoked an NMDAR-dependent initial burst followed by an afterhyperpolarization-induced pause. Phasic release of DA itself evoked acute changes in CIN firing. In particular, in CINs without an initial burst, phasic DA release evoked a pause through D2-type DA receptor activation. Independently, phasic DA activated a slow depolarizing conductance and the late burst through a D1-type DA receptor pathway. In summary, DAergic neurons elicit transient subsecond firing responses in CINs by sequential activation of NMDA, D2-type, and D1-type receptors. This fast control of striatal cholinergic tone by phasic DA provides a novel dynamic link of two transmitter systems central to the detection and selection of relevant stimuli.
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wieland
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Du
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany.
authors.forename: Manfred J
authors.initials: MJ
authors.lastname: Oswald
authors.affiliation: Department of Molecular Biology of the Cell I, DKFZ-ZMBH Alliance and Institute of Anatomy and Cell Biology, Heidelberg University, 69120 Heidelberg, and Institute of Applied Physiology, University of Ulm, 89081 Ulm, Germany.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Parlato
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Köhr
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany, wolfgang.kelsch@zi-mannheim.de.
authors.forename: Wolfgang
authors.identifier: http://orcid.org/0000-0002-3470-8125
authors.initials: W
authors.lastname: Kelsch
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000502:physiology; D059329:Cholinergic Neurons / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000502:physiology*; D007150:Immunohistochemistry; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate
keywords: cholinergic interneurons; glutamate corelease; olfactory tubercle; pause response; phasic dopamine; striatum