title: Dopaminergic modulation of mitral cells and odor responses in the zebrafish olfactory bulb.
abstract: In the olfactory bulb, the modulatory neurotransmitter dopamine (DA) is coexpressed with GABA by local interneurons, but its role in odor processing remains obscure. We examined functions of DA mediated by D₂-like receptors in the olfactory bulb of adult zebrafish by pharmacology, whole-cell recordings, calcium imaging, and optogenetics. Bath application of DA had no detectable effect on odorant-evoked sensory input. DA directly hyperpolarized mitral cells (MCs) via D₂-like receptors and slightly increased their response gain. Consistent with this effect on input-output functions of MCs, small odorant responses were suppressed, whereas strong responses were enhanced in the presence of DA. These effects increased the root-mean-square contrast of population activity patterns but did not reduce their correlations. Optical stimulation of interneurons expressing channelrhodopsin-2 evoked fast GABAergic inhibitory currents in mitral cells but failed to activate D₂ receptor-mediated currents when stimuli were short. Prolonged stimulus trains, however, activated a slow hyperpolarizing current that was blocked by an antagonist of D₂-like receptors. GABA and DA are therefore both released from interneurons by electrical activity and hyperpolarize MCs, but D₂-dependent dopaminergic effects occur on slower timescales. Additional effects of DA may be mediated by D₁-like receptors. These results indicate that DA acts on D₂-like receptors via asynchronous release and/or volume transmission and implicate DA in the slow adaptation of circuit function. The shift of the membrane potential away from spike threshold could adapt mitral cells to background input without compromising their sensitivity.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Sebastian T
authors.initials: ST
authors.lastname: Bundschuh
authors.forename: Peixin
authors.initials: P
authors.lastname: Zhu
authors.forename: Yan-Ping Zhang
authors.initials: YP
authors.lastname: Schärer
authors.forename: Rainer W
authors.initials: RW
authors.lastname: Friedrich
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D065127:Dopamine D2 Receptor Antagonists; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008959:Models, Neurological; D057054:Molecular Imaging / Q000379:methods; D009830:Olfactory Bulb / Q000187:drug effects / Q000502:physiology*; D055696:Olfactory Perception / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010775:Photic Stimulation / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D013268:Stimulation, Chemical; D013997:Time Factors; D015027:Zebrafish
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D012243:Rhodopsin; D004298:Dopamine