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Réjean Dubuc

Publications and source records attributed to Réjean Dubuc.

9 recordsLinked to original sources

Descending GABAergic projections to the mesencephalic locomotor region in the lamprey Petromyzon marinus.

The mesencephalic locomotor region (MLR) plays a significant role in the control of locomotion in all vertebrate species investigated. Forebrain neurons are likely to modulate MLR activity, but little is known about their inputs. Descending GABAergic projections to the MLR were identified by double-labeling neurons using Neurobiotin injected into the MLR combined with immunofluorescence against GABA. Several GABAergic projections to the MLR were identified in the telencephalon and diencephalon. The most abundant GABAergic projection to the MLR came from the caudal portion of the medial pallium, a region that may have similarities with the amygdala of higher vertebrates. A small population of GABAergic cells projecting to the MLR was found in the striatum and the ventral portion of the lateral pallium, which could respectively correspond to the input and output components of the basal ganglia thought to be involved in the selection of motor programs. Other GABAergic projections were found to come from the thalamus and the hypothalamus, which could take part in the motivational aspect of motor behavior in lampreys. Electrophysiological experiments were also carried out to examine the effects of GABA agonists and antagonists injected into the MLR in a semi-intact lamprey preparation. The GABA agonist inhibited locomotion, whereas the GABA antagonist initiated it. These results suggest that the GABAergic projections to the MLR modulate the activity of MLR neurons, which would be inhibited by GABA at rest.

Afferent Pathways↗

Ontogeny of 5-HT neurons in the brainstem of the lamprey, Petromyzon marinus.

This study examined the spatial and temporal distribution of serotonin-immunoreactive (5-HT-ir) neurons in the brainstem of Petromyzon marinus at three developmental stages, larval, postmetamorphic, and reproductive. Computer-assisted 3-D reconstructions were made of the three main 5-HT-ir neuron groups. The rostralmost brainstem group was located near the posterior commissure, the second group at the isthmus, and the third group in the bulbar area. For each of those groups, the distribution of the 5-HT-ir neurons was very similar in the three developmental stages examined, suggesting that the 5-HT system is relatively mature early in larval animals. The soma of 5-HT-ir neurons increased in size and their dendritic fields increased in complexity with development. Furthermore, the number of 5-HT-ir neurons in each group increased significantly from the larval to the reproductive stage. To determine whether this was due to the genesis of 5-HT neurons, bromodeoxyuridine (BrdU) was injected into larval, metamorphosing, and postmetamorphic lampreys. These experiments revealed a few neurons colocalizing BrdU and 5-HT in metamorphosing animals. Taken together, the present results suggest that 5-HT neurons increase in number during maturation and that neurogenesis could, at least partially, contribute to the appearance of new 5-HT cells at different developmental stages.

Animals↗

Dynamic sensorimotor interactions in locomotion.

Locomotion results from intricate dynamic interactions between a central program and feedback mechanisms. The central program relies fundamentally on a genetically determined spinal circuitry (central pattern generator) capable of generating the basic locomotor pattern and on various descending pathways that can trigger, stop, and steer locomotion. The feedback originates from muscles and skin afferents as well as from special senses (vision, audition, vestibular) and dynamically adapts the locomotor pattern to the requirements of the environment. The dynamic interactions are ensured by modulating transmission in locomotor pathways in a state- and phase-dependent manner. For instance, proprioceptive inputs from extensors can, during stance, adjust the timing and amplitude of muscle activities of the limbs to the speed of locomotion but be silenced during the opposite phase of the cycle. Similarly, skin afferents participate predominantly in the correction of limb and foot placement during stance on uneven terrain, but skin stimuli can evoke different types of responses depending on when they occur within the step cycle. Similarly, stimulation of descending pathways may affect the locomotor pattern in only certain phases of the step cycle. Section ii reviews dynamic sensorimotor interactions mainly through spinal pathways. Section iii describes how similar sensory inputs from the spinal or supraspinal levels can modify locomotion through descending pathways. The sensorimotor interactions occur obviously at several levels of the nervous system. Section iv summarizes presynaptic, interneuronal, and motoneuronal mechanisms that are common at these various levels. Together these mechanisms contribute to the continuous dynamic adjustment of sensorimotor interactions, ensuring that the central program and feedback mechanisms are congruous during locomotion.

Animals↗

Modulatory effect of substance P to the brain stem locomotor command in lampreys.

Substance P initiates locomotion when injected in the brain stem of mammals. This study examined the possible role of this peptide on the supraspinal locomotor command system in lampreys. Substance P was bath applied or locally injected into an in vitro isolated brain stem, and the effects of the drug were examined on reticulospinal cells and on the occurrence of swimming in a semi-intact preparation. Bath applications of substance P induced sustained depolarizations occurring rhythmically in intracellularly recorded reticulospinal cells. Spiking activity was superimposed on the depolarizations and swimming was induced. The sustained depolarizations were abolished by tetrodotoxin, and substance P did not affect the membrane resistance of reticulospinal cells nor their firing properties, suggesting that it did not directly effect reticulospinal cells. To establish where the effects were exerted, successive lesions of the brain stem were made as well as local applications of the drug in the brain stem. Removing the mesencephalon abolished the sustained depolarizations, whereas large ejections of the drug in the mesencephalon excited reticulospinal cells and elicited bouts of swimming. More local injections into the mesencephalic locomotor region (MLR) also elicited swimming. After an injection of substance P, the current threshold needed to induce locomotion by MLR stimulation was decreased, and the size of the postsynaptic responses of reticulospinal cells to MLR stimulation was increased. Substance P also reduced the frequency of miniature spontaneous postsynaptic currents in reticulospinal cells. Taken together, these results suggest that substance P plays a neuromodulatory role on the brain stem locomotor networks of lampreys.

Action Potentials↗

Immunohistochemical distribution of tachykinins in the CNS of the lamprey Petromyzon marinus.

The presence of tachykinins in the CNS of vertebrates has been known for many decades, and numerous studies have described their distribution in mammals. Tachykinins were also reported in the CNS of lampreys using immunohistochemistry, chromatography, and radioimmunoassay methods, but the use of substance P (SP)-specific antibodies to reveal those tachykinins could have led to an underestimation of their number in this genus. Therefore, we carried out a new immunohistochemical study on Petromyzon marinus using a commercial polyclonal antibody that binds not only to mammalian SP, but also to other neurokinins. This antibody labeled all previously described lamprey tachykinin-containing neuronal populations, but more important, labeled new populations in several parts of the brain. These include the dorsal gray of the rostral spinal cord, the dorsal column nuclei, the octavolateral area, the nucleus of the solitary tract, the medial rhombencephalic reticular formation, the lateral tegmentum of the rostral rhombencephalon, the torus semicircularis, the optic tectum, the habenula, the mammillary area, the dorsal thalamic area, the lateral hypothalamus, and the septum area. Preabsorption experiments confirmed the binding of the antibody to neurokinins and allowed us to propose that the CNS of P. marinus contains at least two different tachykinins.

Animals↗

Muscarinic modulation of the trigemino-reticular pathway in lampreys.

In lampreys, reticulospinal neurons integrate sensory inputs to adapt their control onto the spinal locomotor networks. Whether and how sensory inputs to reticulospinal neurons are modulated remains to be determined. We showed recently that cholinergic inputs onto reticulospinal neurons play a key role in the initiation of locomotion elicited by stimulation of the mesencephalic locomotor region in semi intact lampreys. Here, we examined the possible role of muscarinic acetylcholine receptors in modulating trigeminal inputs to reticulospinal neurons. A local application of muscarinic agonists onto an intracellularly recorded reticulospinal cell depressed the disynaptic responses to trigeminal stimulation. A depression was also observed when muscarinic agonists were pressure ejected over the brain stem region containing second-order neurons relaying trigeminal inputs to reticulospinal neurons. Conversely, muscarinic antagonists increased the trigeminal-evoked responses, suggesting that a muscarinic depression of sensory inputs to RS neurons is exerted tonically. The muscarinic modulation affected predominantly the N-methyl-d-aspartate (NMDA) component of the trigeminal-evoked responses. Moreover, atropine perfusion facilitated the occurrence of sustained depolarizations induced by stimulation of the trigeminal nerve, and it revealed NMDA-induced intrinsic oscillations in reticulospinal neurons. The functional significance of a muscarinic modulation of a sensory transmission to reticulospinal neurons is discussed.

Afferent Pathways↗

Differential contribution of reticulospinal cells to the control of locomotion induced by the mesencephalic locomotor region.

In lampreys as in other vertebrates, the reticulospinal (RS) system relays inputs from the mesencephalic locomotor region (MLR) to the spinal locomotor networks. Semi-intact preparations of larval sea lamprey were used to determine the relative contribution of the middle (MRRN) and the posterior (PRRN) rhombencephalic reticular nuclei to swimming controlled by the MLR. Intracellular recordings were performed to examine the inputs from the MLR to RS neurons. Stimulation of the MLR elicited monosynaptic excitatory responses of a higher magnitude in the MRRN than in the PRRN. This differential effect was not attributed to intrinsic properties of RS neurons. Paired recordings showed that at threshold intensity for swimming, spiking activity was primarily elicited in RS cells of the MRRN. Interestingly, cells of the PRRN began to discharge at higher stimulation intensities only when MRRN cells had reached their maximal discharge rate. Glutamate antagonists were ejected in either nucleus to reduce their activity. Ejections over the MRRN increased the stimulation threshold for evoking locomotion and resulted in a marked decrease in the swimming frequency and the strength of the muscle contractions. Ejections over the PRRN decreased the frequency of swimming. This study provides support for the concept that RS cells show a specific recruitment pattern during MLR-induced locomotion. RS cells in the MRRN are primarily involved in initiation and maintenance of low-intensity swimming. At higher frequency locomotor rhythm, RS cells in both the MRRN and the PRRN are recruited.

Action Potentials↗

Bimodal locomotion elicited by electrical stimulation of the midbrain in the salamander Notophthalmus viridescens.

The present experiments were designed to identify the mesencephalic locomotor region (MLR) in the salamander. An in vitro semi-intact preparation from a decerebrate adult salamander (Notophthalmus viridescens) was developed in which the locomotor activities were monitored from electromyographic and video recordings. The results show that the two locomotor modes exhibited by salamanders (i.e., stepping and swimming) were evoked by electrical microstimulation (5-15 Hz; 0.1-10 microA; 2 msec pulses) of a circumscribed region in the caudal mesencephalon. At threshold current strength (0.5-3.5 microA at 15 Hz), rhythmic limb movements and intersegmental coordination, such as during stepping, were induced. As the stimulation strength was subsequently increased, the frequency of stepping became more rapid, and, at 2.0-5.5 microA, the limbs were held back against the body wall and swimming movements of the trunk were induced. An additional increase of the stimulation strength induced an increase of the frequency and amplitude of the swimming movements. Anatomical studies conducted in parallel revealed the presence of choline acetyltransferase immunoreactive cells in the functionally identified MLR region. Together, the present results indicate that the MLR is present in salamanders and that its level of activation determines the mode of locomotion. Walking is induced at low activation levels, and swimming, which constitutes a faster mode of locomotion, requires stronger stimulation of the MLR. Furthermore, as in other vertebrates, the MLR contains cholinergic cells.

Animals↗

Nicotinic activation of reticulospinal cells involved in the control of swimming in lampreys.

In lampreys as in other vertebrates, brainstem centres play a key role in the initiation and control of locomotion. One such centre, the mesencephalic locomotor region (MLR), was identified physiologically at the mesopontine border. Descending inputs from the MLR are relayed by reticulospinal neurons in the pons and medulla, but the mechanisms by which this is carried out remain unknown. Because previous studies in higher vertebrates and lampreys described cholinergic cells within the MLR region, we investigated the putative role of cholinergic agonists in the MLR-controlled locomotion. The local application of either acetylcholine or nicotine exerted a direct dose-dependent excitation on reticulospinal neurons as well as induced active or fictive locomotion. It also accelerated ongoing fictive locomotion. Choline acetyltransferase-immunoreactive cells were found in the region identified as the MLR of lampreys and nicotinic antagonists depressed, whereas physostigmine enhanced the compound EPSP evoked in reticulospinal neurons by electrical stimulation of this region. In addition, cholinergic inputs from the MLR to reticulospinal neurons were found to be monosynaptic. When the brainstem was perfused with d-tubocurarine, the induction of swimming by MLR stimulation was depressed, but not prevented, in a semi-intact preparation. Altogether, the results support the hypothesis that cholinergic inputs from the MLR to reticulospinal cells play a substantial role in the initiation and the control of locomotion.

Acetylcholine↗