Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human

Abstract

In vertebrates, dopamine neurons are classically known to modulate locomotion via their ascending projections to the basal ganglia that project to brainstem locomotor networks. An increased dopaminergic tone is associated with increase in locomotor activity. In pathological conditions where dopamine cells are lost, such as in Parkinson's disease, locomotor deficits are traditionally associated with the reduced ascending dopaminergic input to the basal ganglia. However, a descending dopaminergic pathway originating from the substantia nigra pars compacta was recently discovered. It innervates the mesencephalic locomotor region (MLR) from basal vertebrates to mammals. This pathway was shown to increase locomotor output in lampreys, and could very well play an important role in mammals. Here, we provide a detailed account on the newly found dopaminergic pathway in lamprey, salamander, rat, monkey, and human. In lampreys and salamanders, dopamine release in the MLR is associated with the activation of reticulospinal neurons that carry the locomotor command to the spinal cord. Dopamine release in the MLR potentiates locomotor movements through a D1-receptor mechanism in lampreys. In rats, stimulation of the substantia nigra pars compacta elicited dopamine release in the pedunculopontine nucleus, a known part of the MLR. In a monkey model of Parkinson's disease, a reduced dopaminergic innervation of the brainstem locomotor networks was reported. Dopaminergic fibers are also present in human pedunculopontine nucleus. We discuss the conserved locomotor role of this pathway from lamprey to mammals, and the hypothesis that this pathway could play a role in the locomotor deficits reported in Parkinson's disease.

Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

“…The mechanism responsible for a reduction in locomotor activity which occurs in old rats is still not well clarified. However, several reports suggest that extracellular levels of dopamine are reduced in the old animals (Greenwood, Lin, Sundararajan, Fryxell, & Parasuraman, ; Keeler, Lallemand, Patel, Castro Brás, & Clemens, ; Zucca et al, ) and this neurotransmitter is critical in locomotor activity (for review see Flores, Morales‐Medina, et al, ; Ryczko & Dubuc, ; Sharples, Koblinger, Humphreys, & Whelan, ). In addition, locomotor activity in a novel environment involved the participation of the NAcc and indicated how the rat responded to moderate stress (for review see Flores, Flores‐Gómez, et al, ; Flores, Morales‐Medina, et al, ; Ikemoto & Panksepp, ).…”

“…In addition, locomotor activity in a novel environment involved the participation of the NAcc and indicated how the rat responded to moderate stress (for review see Flores, Flores‐Gómez, et al, ; Flores, Morales‐Medina, et al, ; Ikemoto & Panksepp, ). However, several reports also suggest that other neurotransmitters may participate in the control of locomotor activity, such as glutamate, GABA, and serotonin (For review see Flores, Morales‐Medina, et al, ; Melancon, Lorrain, & Dionne, ; Ryczko & Dubuc, ). On the other hand, we did not find morphological changes in the NAcc in the pregnant rats; however, rats with two pregnancies also showed an increase in the number of dendritic spine in the PFC and CA1 of the dorsal hippocampus, which would suggest that this increase in locomotor activity could not be mediated by the NAcc.…”

Current Principles of Motor Control, with Special Reference to Vertebrate Locomotion

“…MLR is present in vertebrates extending from lamprey to primates (81,132,331,358,397,413,418,419) and is thus a conserved command structure controlling locomotion in tetrapods as well as swimmers. MLR (see FIGURE 9) at the mesopontine area is located close to both the cuneiform nucleus and the pedunculopontine nucleus (PPN).…”

Neural correlates of state transitions elicited by a chemosensory danger cue

“…The significance of sustained 281 activity in posterior tuberculum, which contains dopaminergic neurons [18,54], is 282 unclear. The nucleus in basal vertebrates is proposed to send both ascending and 283 descending projections that disinhibit the downstream targets to initiate 284 locomotion [46]. Further investigations are needed to dissect the relationship between 285 the activity profile of the posterior tuberculum evoked by the alarm substance and the 286 larval behavior reported here.…”