Specific neural substrate linking respiration to locomotion

Gariépy, Jean-François; Missaghi, Kianoush; Chevallier, Stéphanie; Chartré, Shannon; Robert, Maxime; Auclair, François; Lund, James P.; Dubuc, Réjean

doi:10.1073/pnas.1113002109

Cited by 54 publications

(70 citation statements)

References 55 publications

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“…Chemical stimulation of the PT with local microinjections of 3.0 to 8.0 pmol of D-glutamate (5 mM, 17-43 pulses of 20 ms, 0.6-1.6 nL per microinjection) into the site used for electrical stimulation, was confirmed to elicit locomotion and reticulospinal discharges in one preparation. This is consistent with previous observations that electrical or chemical stimulation with D-glutamate of this region initiates locomotion (10,11). By using targeted whole-cell patch clamp recordings in an isolated brain preparation (Materials and Methods), we found that trains of stimuli (10-s train, 4-5 Hz, 10-35 μA, 2-ms pulses) to the PT (Fig.…”

Section: Significancesupporting

confidence: 77%

“…Locomotor movements of body were recorded (30 frames per second) by a video camera (HDR-XR200; Sony) positioned 1 m above the recording chamber. Locomotor movements were tracked and analyzed by using custom written scripts in Matlab (MathWorks) previously used in our laboratory (11,35). Briefly, tracking markers were equidistantly distributed along the midline of the body by using geometrical analysis of the body.…”

Section: Methodsmentioning

confidence: 99%

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Forebrain dopamine neurons project down to a brainstem region controlling locomotion

Ryczko

Grätsch

Auclair

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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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.motor system | Parkinson disease D opamine (DA) neurons of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) modulate motor behaviors, including locomotion, through ascending projections to the basal ganglia, the output of which projects to the mesencephalic locomotor region (MLR) (1-3), a brainstem region known to control locomotion in all vertebrate species tested to date (reviewed in ref. 4). DA is known to control the excitability of striatal cells, and a dysfunction of the ascending DA pathway to the striatum is considered to be the main cause for the motor deficits in Parkinson disease (1). However, there have been hints of descending DA projections that would be in position to directly modulate the MLR and hence locomotor activity. In monkeys, DA terminals of unknown origin were observed in the pedunculopontine nucleus (PPN) (5), considered part of the MLR (reviewed in ref. 4). In addition, there is an axonal projection from the SNc to the PPN in rats, but the transmitter system is unknown (6).We examined the DA system in a basal vertebrate, the lamprey, and found a previously unknown descending DA pathway from the posterior tuberculum (PT) to the MLR, which comprises the PPN and the laterodorsal tegmental nucleus (LDT) in lampreys (ref. 7; reviewed...

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Section: Significancesupporting

confidence: 77%

Section: Methodsmentioning

confidence: 99%

Forebrain dopamine neurons project down to a brainstem region controlling locomotion

Ryczko

Grätsch

Auclair

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…The procedure was similar to that previously used in lampreys (22,57,58) and salamanders (7). Biocytin (Sigma-Aldrich B-4261) and TRDA (Molecular Probes D-3328) were used for retrograde tracing.…”

Section: Methodsmentioning

confidence: 99%

A descending dopamine pathway conserved from basal vertebrates to mammals

Ryczko

Cone

Alpert

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Dopamine neurons are classically known to modulate locomotion indirectly through ascending projections to the basal ganglia that project down to brainstem locomotor networks. Their loss in Parkinson's disease is devastating. In lampreys, we recently showed that brainstem networks also receive direct descending dopaminergic inputs that potentiate locomotor output. Here, we provide evidence that this descending dopaminergic pathway is conserved to higher vertebrates, including mammals. In salamanders, dopamine neurons projecting to the striatum or brainstem locomotor networks were partly intermingled. Stimulation of the dopaminergic region evoked dopamine release in brainstem locomotor networks and concurrent reticulospinal activity. In rats, some dopamine neurons projecting to the striatum also innervated the pedunculopontine nucleus, a known locomotor center, and stimulation of the dopaminergic region evoked pedunculopontine dopamine release in vivo. Finally, we found dopaminergic fibers in the human pedunculopontine nucleus. The conservation of a descending dopaminergic pathway across vertebrates warrants re-evaluating dopamine's role in locomotion.D opaminergic neurons represent a vital neuromodulatory component essential for vertebrate motor control, and their loss in neurodegenerative disease is devastating. The meso-diencephalic dopamine (DA) neurons are known to provide ascending projections to the basal ganglia, which, in turn, provide input to cortical structure in mammals but also project caudally to the mesencephalic locomotor region (MLR), a highly conserved structure that controls locomotion in all vertebrates investigated to date (1-7; for review, see ref. 8). A growing body of evidence supports the view that basal ganglia connectivity is highly conserved among vertebrates, from lampreys to mammals (9-11; for review, see ref. 12), with some interspecies differences recently highlighted (13). As such, the homology between DA cell populations remains to be resolved in vertebrates. As a general rule, DA neurons from the meso-diencephalon send projections to the striatum in all vertebrates. In lampreys and teleosts, those neurons are located only in the diencephalon (posterior tuberculum), but in tetrapods and cartilaginous fishes (14) they are located in both the diencephalon and the mesencephalon. An increasing number of authors seem to agree with the hypothesis that at least some of the mesodiencephalic DA neurons located in the diencephalon are homologous in all vertebrates, and thus, homologous to at least a portion of the mammalian substantia nigra pars compacta (SNc)/ ventral tegmental area (VTA) (13, 15-19; for review, see ref. 20). Alternatively, it was suggested that the posterior tuberculum DA neurons projecting to the striatum in zebrafish are homologs of the mammalian DA neurons of the A11 group (21). This will be discussed below in light of the results of the present study.In lampreys, only a few meso-diencephalic DA neurons send ascending projections to the striatum (9, 22); the majority ...

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“…Afferent input to the investigated regions may also arise from structures within the central nervous system that are known to influence the respiratory activity, such as the neural system that is involved in triggering both locomotion and increases in respiratory activity in response to internal cues in specific behavioral contexts, such as exploration, food seeking, reproduction and defense reaction. These mechanisms rely on supraspinal structures and involve neurons of the mesencephalic locomotor region (Garie´py et al, 2010(Garie´py et al, , 2012b. We cannot exclude that components of this neural system may operate by removing an inhibitory control on both the respiratory motoneuron region and the OLA.…”

Section: Functional Considerationsmentioning

confidence: 99%

Inhibitory control of ascending glutamatergic projections to the lamprey respiratory rhythm generator

et al. 2016

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Abstract-Neurons within the vagal motoneuron region of the lamprey have been shown to modulate respiratory activity via ascending excitatory projections to the paratrigeminal respiratory group (pTRG), the proposed respiratory rhythm generator. The present study was performed on in vitro brainstem preparations of the lamprey to provide a characterization of ascending projections within the whole respiratory motoneuron column with regard to the distribution of neurons projecting to the pTRG and related neurochemical markers. Injections of Neurobiotin were performed into the pTRG and the presence of glutamate, GABA and glycine immunoreactivity was investigated by doublelabeling experiments. Interestingly, retrogradely labeled neurons were found not only in the vagal region, but also in the facial and glossopharyngeal motoneuron regions. They were also present within the sensory octavolateral area (OLA). The results show for the first time that neurons projecting to the pTRG are immunoreactive for glutamate, surrounded by GABA-immunoreactive structures and associated with the presence of glycinergic cells. Consistently, GABA A or glycine receptor blockade within the investigated regions increased the respiratory frequency. Furthermore, microinjections of agonists and antagonists of ionotropic glutamate receptors and of the GABA A receptor agonist muscimol showed that OLA neurons do not contribute to respiratory rhythm generation. The results provide evidence that glutamatergic ascending pathways to the pTRG are subject to a potent inhibitory control and suggest that disinhibition is one important mechanism subserving their function. The general characteristics of inhibitory control involved in rhythmic activities, such as respiration, appear to be highly conserved throughout vertebrate evolution.

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Specific neural substrate linking respiration to locomotion

Abstract: PERSPECTIVECorrection for "The role of terrestrially derived organic carbon in the coastal ocean: A changing paradigm and the priming effect,"

Cited by 54 publications

References 55 publications

Forebrain dopamine neurons project down to a brainstem region controlling locomotion

Forebrain dopamine neurons project down to a brainstem region controlling locomotion

A descending dopamine pathway conserved from basal vertebrates to mammals

Inhibitory control of ascending glutamatergic projections to the lamprey respiratory rhythm generator

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