Brainstem neural mechanisms controlling locomotion with special reference to basal vertebrates

Over the last 60 years, the basic neural circuitry responsible for the supraspinal control of locomotion has progressively been uncovered. Initially, significant progress was made in identifying the different supraspinal structures controlling locomotion in mammals as well as some of the underlying mechanisms. It became clear, however, that the complexity of the mammalian central nervous system (CNS) prevented researchers from characterizing the detailed cellular mechanisms involved and that animal models with a simpler nervous system were needed. Basal vertebrate species such as lampreys, xenopus embryos, and zebrafish became models of choice. More recently, optogenetic approaches have considerably revived interest in mammalian models. The mesencephalic locomotor region (MLR) is an important brainstem region known to control locomotion in all vertebrate species examined to date. It controls locomotion through intermediary cells in the hindbrain, the reticulospinal neurons (RSNs). The MLR comprises populations of cholinergic and glutamatergic neurons and their specific contribution to the control of locomotion is not fully resolved yet. Moreover, the downward projections from the MLR to RSNs is still not fully understood. Reporting on discoveries made in different animal models, this review article focuses on the MLR, its projections to RSNs, and the contribution of these neural elements to the control of locomotion. Excellent and detailed reviews on the brainstem control of locomotion have been recently published with emphasis on mammalian species. The present review article focuses on findings made in basal vertebrates such as the lamprey, to help direct new research in mammals, including humans

PRISMA: a new model of integrated service delivery for the frail older people in Canada

PURPOSE: PRISMA is an innovative co-ordination-type Integrated Service Delivery System developed to improve continuity and increase the efficacy and efficiency of services, especially for older and disabled populations. DESCRIPTION: The mechanisms and tools developed and implemented by PRISMA include: (1) co-ordination between decision-makers and managers, (2) a single entry point, (3) a case management process, (4) individualised service plans, (5) a single assessment instrument based on the clients' functional autonomy, and (6) a computerised clinical chart for communicating between institutions for client monitoring purposes. PRELIMINARY RESULTS: The efficacy of this model has been tested in a pilot project that showed a decreased incidence of functional decline, a decreased burden for caregivers and a smaller proportion of older people wishing to be institutionalised. CONCLUSION: The on-going implementation and effectiveness study will show evidence of its real value and its impact on clienteles and cost

Supraspinal control of locomotion

International audienceLocomotion is a basic motor function generated and controlled by genetically defined neuronal networks. The pattern of muscle synergies is generated in the spinal cord, whereas neural centers located above the spinal cord in the brainstem and the forebrain are essential for initiating and controlling locomotor movements. One such locomotor control center in the brainstem is the mesencephalic locomotor region (MLR), first discovered in cats and later found in all vertebrate species tested to date. Over the last years, we have investigated the cellular mechanisms by which this locomotor region operates in lampreys. The lamprey MLR is a well-circumscribed region located at the junction between the midbrain and hindbrain. Stimulation of the MLR induces locomotion with an intensity that increases with the stimulation strength. Glutamatergic and cholinergic monosynaptic inputs from the MLR are responsible for excitation of reticulospinal (RS) cells that in turn activate the spinal locomotor networks. The inputs are larger in the rostral than in the caudal hindbrain RS cells. MLR stimulation on one side elicits symmetrical excitatory inputs in RS cells on both sides, and this is linked to bilateral projections of the MLR to RS cells. In addition to its inputs to RS cells, the MLR activates a well-defined group of muscarinoceptive cells in the brainstem that feeds back strong excitation to RS cells in order to amplify the locomotor output. Finally, the MLR gates sensory inputs to the brainstem through a muscarinic mechanism. It appears therefore that the MLR not only controls locomotor activity but also filters sensory influx during locomotion

The effectiveness of the PRISMA integrated service delivery network: preliminary report on methods and baseline data

Purpose: The PRISMA study analyzes an innovative coordination-type integrated service delivery (ISD) system developed to improve continuity and increase the effectiveness and efficiency of services, especially for older and disabled populations. The objective of the PRISMA study is to evaluate the effectiveness of this system to improve health, empowerment and satisfaction of frail older people, modify their health and social services utilization, without increasing the burden of informal caregivers. The objective of this paper is to present the methodology and give baseline data on the study participants. <br><br> Methods: A quasi-experimental study with pre-test, multiple post-tests, and a comparison group was used to evaluate the impact of PRISMA ISD. Elders at risk of functional decline (501 experimental, 419 control) participated in the study. <br><br> Results: At entry, the two groups were comparable for most variables. Over the first year, when the implementation rate was low (32%), participants from the control group used fewer services than those from the experimental group. After the first year, no significant statistical difference was observed for functional decline and changes in the other outcome variables. <br><br> Conclusion: This first year must be considered a baseline year, showing the situation without significant implementation of PRISMA ISD systems. Results for the following years will have to be examined with consideration of these baseline results

The Neuroanatomical Organization of Projection Neurons Associated with Different Olfactory Bulb Pathways in the Sea Lamprey, Petromyzon marinus

Although there is abundant evidence for segregated processing in the olfactory system across vertebrate taxa, the spatial relationship between the second order projection neurons (PNs) of olfactory subsystems connecting sensory input to higher brain structures is less clear. In the sea lamprey, there is tight coupling between olfaction and locomotion via PNs extending to the posterior tuberculum from the medial region of the olfactory bulb. This medial region receives peripheral input predominantly from the accessory olfactory organ. However, the axons from olfactory sensory neurons residing in the main olfactory epithelium extend to non-medial regions of the olfactory bulb, and the non-medial bulbar PNs extend their axons to the lateral pallium. It is not known if the receptive fields of the PNs in the two output pathways overlap; nor has the morphology of these PNs been investigated. In this study, retrograde labelling was utilized to investigate the PNs belonging to medial and non-medial projections. The dendrites and somata of the medial PNs were confined to medial glomerular neuropil, and dendrites of non-medial PNs did not enter this territory. The cell bodies and dendrites of the non-medial PNs were predominantly located below the glomeruli (frequently deeper in the olfactory bulb). While PNs in both locations contained single or multiple primary dendrites, the somal size was greater for medial than for non-medial PNs. When considered with the evidence-to-date, this study shows different neuroanatomical organization for medial olfactory bulb PNs extending to locomotor control centers and non-medial PNs extending to the lateral pallium in this vertebrate

A neuronal substrate for a state-dependent modulation of sensory inputs in the brainstem

International audienceCentral networks modulate sensory transmission during motor behavior. Sensory inputs may thus have distinct impacts according to the state of activity of the central networks. Using an in-vitro isolated lamprey brainstem preparation, we investigated whether a brainstem locomotor center, the mesencephalic locomotor region (MLR), modulates sensory transmission. The synaptic responses of brainstem reticulospinal (RS) cells to electrical stimulation of the sensory trigeminal nerve were recorded before and after electrical stimulation of the MLR. The RS cell synaptic responses were significantly reduced by MLR stimulation and the reduction of the response increased with the stimulation intensity of the MLR. Bath perfusion of atropine prevented the depression of sensory transmission, indicating that muscarinic receptor activation is involved. Previous studies have shown that, upon stimulation of the MLR, behavioral activity switches from a resting state to an active-locomotor state. Therefore, our results suggest that a state-dependent modulation of sensory transmission to RS cells occurs in the behavioral context of locomotion and that muscarinic inputs from the MLR are involved

Bilateral connectivity in the brainstem respiratory networks of lampreys

This study examines the connectivity in the neural networks controlling respiration in the lampreys, a basal vertebrate. Previous studies have shown that the lamprey paratrigeminal respiratory group (pTRG) plays a crucial role in the generation of respiration. By using a combination of anatomical and physiological techniques, we characterized the bilateral connections between the pTRGs and descending projections to the motoneurons. Tracers were injected in the respiratory motoneuron pools to identify pre‐motor respiratory interneurons. Retrogradely labeled cell bodies were found in the pTRG on both sides. Whole‐cell recordings of the retrogradely labeled pTRG neurons showed rhythmical excitatory currents in tune with respiratory motoneuron activity. This confirmed that they were related to respiration. Intracellular labeling of individual pTRG neurons revealed axonal branches to the contralateral pTRG and bilateral projections to the respiratory motoneuronal columns. Stimulation of the pTRG induced excitatory postsynaptic potentials in ipsi‐ and contralateral respiratory motoneurons as well as in contralateral pTRG neurons. A lidocaine HCl (Xylocaine) injection on the midline at the rostrocaudal level of the pTRG diminished the contralateral motoneuronal EPSPs as well as a local injection of 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and (2R)‐amino‐5‐phosphonovaleric acid (AP‐5) on the recorded respiratory motoneuron. Our data show that neurons in the pTRG send two sets of axonal projections: one to the contralateral pTRG and another to activate respiratory motoneurons on both sides through glutamatergic synapses

A Cellular Mechanism for the Transformation of a Sensory Input into a Motor Command

International audienceThe initiation and control of locomotion largely depend on processing of sensory inputs. The cellular bases of locomotion have been extensively studied in lampreys where reticulospinal (RS) neurons constitute the main descending system activating and controlling the spinal locomotor networks. Ca 2ϩ imaging and intracellular recordings were used to study the pattern of activation of RS neurons in response to cutaneous stimulation. Pressure applied to the skin evoked a linear input/output relationship in RS neurons until a threshold level, at which a depolarizing plateau was induced, the occurrence of which was associated with the onset of swimming activity in a semi-intact preparation. The occurrence of a depolarizing plateau was abolished by blocking the NMDA receptors that are located on RS cells. Moreover, the depolarizing plateaus were accompanied by a rise in [Ca 2ϩ ] i , and an intracellular injection of the Ca 2ϩ chelator BAPTA into single RS cells abolished the plateaus, suggesting that the latter are Ca 2ϩ dependent and rely on intrinsic properties of RS cells. The plateaus were shown to result from the activation of a Ca 2ϩ-activated nonselective cation current that maintains the cell in a depolarized state. It is concluded that this intrinsic property of the RS neuron is then responsible for the transformation of an incoming sensory signal into a motor command that is then forwarded to the spinal locomotor networks

Sensory Activation of Command Cells for Locomotion and Modulatory Mechanisms: Lessons from Lampreys

Sensorimotor transformation is one of the most fundamental and ubiquitous functions of the central nervous system. Although the general organization of the locomotor neural circuitry is relatively well understood, less is known about its activation by sensory inputs and its modulation. Utilizing the lamprey model, a detailed understanding of sensorimotor integration in vertebrates is emerging. In this article, we explore how the vertebrate central nervous system integrates sensory signals to generate motor behavior by examining the pathways and neural mechanisms involved in the transformation of cutaneous and olfactory inputs into motor output in the lamprey. We then review how 5-HT acts on these systems by modulating both sensory inputs and motor output. A comprehensive review of this fundamental topic should provide a useful framework in the fields of motor control, sensorimotor integration and neuromodulation

A brainstem neural substrate for stopping locomotion

Locomotion occurs sporadically and needs to be started, maintained, and stopped. The neural substrate underlying the activation of locomotion is partly known, but little is known about mechanisms involved in termination of locomotion. Recently, reticulospinal neurons (stop cells) were found to play a crucial role in stopping locomotion in the lamprey: their activation halts ongoing locomotion and their inactivation slows down the termination process. Intracellular recordings of these cells revealed a distinct activity pattern, with a burst of action potentials at the beginning of a locomotor bout and one at the end (termination burst). The termination burst was shown to be time linked to the end of locomotion, but the mechanisms by which it is triggered have remained unknown. We studied this in larval sea lampreys (Petromyzon marinus; the sex of the animals was not taken into account). We found that the mesencephalic locomotor region (MLR), which is known to initiate and control locomotion, stops ongoing locomotion by providing synaptic inputs that trigger the termination burst in stop cells. When locomotion is elicited by MLR stimulation, a second MLR stimulation stops the locomotor bout if it is of lower intensity than the initial stimulation. This occurs for MLR-induced, sensory-evoked, and spontaneous locomotion. Furthermore, we show that glutamatergic and, most likely, monosynaptic projections from the MLR activate stop cells during locomotion. Therefore, activation of the MLR not only initiates locomotion, but can also control the end of a locomotor bout. These results provide new insights onto the neural mechanisms responsible for stopping locomotion.SIGNIFICANCE STATEMENT The mesencephalic locomotor region (MLR) is a brainstem region well known to initiate and control locomotion. Since its discovery in cats in the 1960s, the MLR has been identified in all vertebrate species tested from lampreys to humans. We now demonstrate that stimulation of the MLR not only activates locomotion, but can also stop it. This is achieved through a descending glutamatergic signal, most likely monosynaptic, from the MLR to the reticular formation that activates reticulospinal stop cells. Together, our findings have uncovered a neural mechanism for stopping locomotion and bring new insights into the function of the MLR