title: Forebrain dopamine neurons project down to a brainstem region controlling locomotion.
abstract: The contribution of dopamine (DA) to locomotor control is traditionally attributed to ascending dopaminergic projections from the substantia nigra pars compacta and the ventral tegmental area to the basal ganglia, which in turn project down to the mesencephalic locomotor region (MLR), a brainstem region controlling locomotion in vertebrates. However, a dopaminergic innervation of the pedunculopontine nucleus, considered part of the MLR, was recently identified in the monkey. The origin and role of this dopaminergic input are unknown. We addressed these questions in a basal vertebrate, the lamprey. Here we report a functional descending dopaminergic pathway from the posterior tuberculum (PT; homologous to the substantia nigra pars compacta and/or ventral tegmental area of mammals) to the MLR. By using triple labeling, we found that dopaminergic cells from the PT not only project an ascending pathway to the striatum, but send a descending projection to the MLR. In an isolated brain preparation, PT stimulation elicited excitatory synaptic inputs into patch-clamped MLR cells, accompanied by activity in reticulospinal cells. By using voltammetry coupled with electrophysiological recordings, we demonstrate that PT stimulation evoked DA release in the MLR, together with the activation of reticulospinal cells. In a semi-intact preparation, stimulation of the PT elicited reticulospinal activity together with locomotor movements. Microinjections of a D1 antagonist in the MLR decreased the locomotor output elicited by PT stimulation, whereas injection of DA had an opposite effect. It appears that this descending dopaminergic pathway has a modulatory role on MLR cells that are known to receive glutamatergic projections and promotes locomotor output.
authors.affiliation: Groupe de Recherche sur le Système Nerveux Central, Département de Physiologie, Université de Montréal, Montréal, QC, Canada H3C 3J7.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Ryczko
authors.forename: Swantje
authors.initials: S
authors.lastname: Grätsch
authors.forename: François
authors.initials: F
authors.lastname: Auclair
authors.forename: Catherine
authors.initials: C
authors.lastname: Dubé
authors.forename: Saskia
authors.initials: S
authors.lastname: Bergeron
authors.forename: Michael H
authors.initials: MH
authors.lastname: Alpert
authors.forename: Jackson J
authors.initials: JJ
authors.lastname: Cone
authors.forename: Mitchell F
authors.initials: MF
authors.lastname: Roitman
authors.forename: Simon
authors.initials: S
authors.lastname: Alford
authors.forename: Réjean
authors.initials: R
authors.lastname: Dubuc
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001933:Brain Stem / Q000166:cytology / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000166:cytology*; D008124:Locomotion / Q000502:physiology*; D008856:Microscopy, Fluorescence; D056347:Neuroanatomical Tract-Tracing Techniques; D018408:Patch-Clamp Techniques; D048428:Petromyzon / Q000033:anatomy & histology / Q000502:physiology*; D016548:Prosencephalon / Q000166:cytology*; D017447:Receptors, Dopamine D1 / Q000378:metabolism
chemical_list: D017447:Receptors, Dopamine D1
keywords: Parkinson disease; motor system
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