Origin of excitatory drive to a spinal locomotor network

Roberts, Alan; Li, Wen-Chang; Soffe, Stephen R; Wolf, Ervin

doi:10.1016/j.brainresrev.2007.06.015

Cited by 55 publications

(53 citation statements)

References 30 publications

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“…However, the use of constant stimulation precludes separation of the mechanisms intrinsic to the spinal circuits from those dependent on descending inputs. The role of descending inputs is unclear as to whether they only provide a "go" signal (Deliagina et al, 2002;Dubuc et al, 2008;Jordan et al, 2008) or whether the descending neurons are involved in the generation of the locomotor rhythm (Chong and Drapeau, 2007;Roberts et al, 2008Roberts et al, , 2010Soffe et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Initiation of Locomotion in Adult Zebrafish

Kyriakatos

Mahmood²,

Ausborn³

et al. 2011

Journal of Neuroscience

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Motor behavior is generated by specific neural circuits. Those producing locomotion are located in the spinal cord, and their activation depends on descending inputs from the brain or on sensory inputs. In this study, we have used an in vitro brainstem-spinal cord preparation from adult zebrafish to localize a region where stimulation of descending inputs can induce sustained locomotor activity. We show that a brief stimulation of descending inputs at the junction between the brainstem and spinal cord induces long-lasting swimming activity. The swimming frequencies induced are remarkably similar to those observed in freely moving adult fish, arguing that the induced locomotor episode is highly physiological. The motor pattern is mediated by activation of ionotropic glutamate and glycine receptors in the spinal cord and is not the result of synaptic interactions between neurons at the site of the stimulation in the brainstem. We also compared the activity of motoneurons during locomotor activity induced by electrical stimulation of descending inputs and by exogenously applied NMDA. Prolonged NMDA application changes the shape of the synaptic drive and action potentials in motoneurons. When escape activity occurs, the swimming activity in the intact zebrafish was interrupted and some of the motoneurons involved became inhibited in vitro. Thus, the descending inputs seem to act as a switch to turn on the activity of the spinal locomotor network in the caudal spinal cord. We propose that recurrent synaptic activity within the spinal locomotor circuits can transform a brief input into a well coordinated and long-lasting swimming pattern.

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Section: Introductionmentioning

confidence: 99%

Initiation of Locomotion in Adult Zebrafish

Kyriakatos

Mahmood²,

Ausborn³

et al. 2011

Journal of Neuroscience

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“…basal ganglia ͉ brainstem ͉ computational model ͉ lamprey ͉ spinal CPG V ertebrate behavior depends on different sets of neuronal networks specialized to coordinate different motor tasks like locomotion, breathing, and the expression of emotions (1)(2)(3)(4)(5). The activity of these networks is governed by brainstem command centers that are, in turn, under the control of the basal ganglia (1,2).…”

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confidence: 99%

Simple cellular and network control principles govern complex patterns of motor behavior

Kozlov

Huss²,

Lansner³

et al. 2009

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

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The vertebrate central nervous system is organized in modules that independently execute sophisticated tasks. Such modules are flexibly controlled and operate with a considerable degree of autonomy. One example is locomotion generated by spinal central pattern generator networks (CPGs) that shape the detailed motor output. The level of activity is controlled from brainstem locomotor command centers, which in turn, are under the control of the basal ganglia. By using a biophysically detailed, full-scale computational model of the lamprey CPG (10,000 neurons) and its brainstem/forebrain control, we demonstrate general control principles that can adapt the network to different demands. Forward or backward locomotion and steering can be flexibly controlled by local synaptic effects limited to only the very rostral part of the network. Variability in response properties within each neuronal population is an essential feature and assures a constant phase delay along the cord for different locomotor speeds.basal ganglia ͉ brainstem ͉ computational model ͉ lamprey ͉ spinal CPG V ertebrate behavior depends on different sets of neuronal networks specialized to coordinate different motor tasks like locomotion, breathing, and the expression of emotions (1-5). The activity of these networks is governed by brainstem command centers that are, in turn, under the control of the basal ganglia (1, 2). Although the critical role of these networks is well established, their intrinsic mode of operation has, for the most part, remained enigmatic. The lamprey nervous system provides one of the few examples in which detailed knowledge is available, not only of the different types of the participating neurons, but also their membrane properties and synaptic connectivity, particularly with regard to the spinal network (6, 7). Even with this knowledge at hand, it is very difficult, if not impossible, to establish, without the help of modeling, whether the experimental data available are actually sufficient to account for the dynamic operation of the networkand enable exploration of the particular role of different cellular and synaptic components to make predictions of their functional role. To achieve this, we report here a biophysically realistic model of the locomotor network and its control from the brain. The spinal network is composed of excitatory and inhibitory model neurons that, in considerable detail, behave as their biological counterparts. It proved to be important to introduce within each pool of model neurons the known biological variability in neuronal size and membrane properties. Thanks to recent developments in computer technology, we have been able to make a full-scale model of the network with 100 model neurons per segment, each of the Hodgkin-Huxley type-altogether 10,000 neurons connected via 760,000 synapses in the 100 segments. We represent the brainstem command system, as well as the forebrain control from the basal ganglia with an additional 3,500 neurons. Simulations limited to subsamples of neurons have previou...

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“…The spinal cord acts as an interface to process descending commands from the brain and sensory inputs from the periphery (5,8,(10)(11)(12)(13)(14)(15)(16). Many insights into the organization and function of circuits underlying motor behavior have been gained from studies of spinal networks controlling locomotor movements (6,13,(17)(18)(19)(20)(21)(22)(23)(24). The basic locomotor activity requires the interplay of ipsilateral excitatory drive and crossed inhibition, which ensures the alternating pattern between the two sides of the spinal cord.…”

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confidence: 99%

Origin of excitation underlying locomotion in the spinal circuit of zebrafish

Eklöf-Ljunggren

Haupt²,

Ausborn³

et al. 2012

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

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Neural circuits in the spinal cord transform instructive signals from the brain into well-coordinated locomotor movements by virtue of rhythm-generating components. Although evidence suggests that excitatory interneurons are the essence of locomotor rhythm generation, their molecular identity and the assessment of their necessity have remained unclear. Here we show, using larval zebrafish, that V2a interneurons represent an intrinsic source of excitation necessary for the normal expression of the locomotor rhythm. Acute and selective ablation of these interneurons increases the threshold of induction of swimming activity, decreases the burst frequency, and alters the coordination of the rostro-caudal propagation of activity. Thus, our results argue that V2a interneurons represent a source of excitation that endows the spinal circuit with the capacity to generate locomotion.central pattern generator | premotor interneurons | motor behavior | synaptic transmission T he generation of motor behavior involves decision making, selection, initiation, and execution (1-9). The spinal cord acts as an interface to process descending commands from the brain and sensory inputs from the periphery (5,8,(10)(11)(12)(13)(14)(15)(16). Many insights into the organization and function of circuits underlying motor behavior have been gained from studies of spinal networks controlling locomotor movements (6,13,(17)(18)(19)(20)(21)(22)(23)(24). The basic locomotor activity requires the interplay of ipsilateral excitatory drive and crossed inhibition, which ensures the alternating pattern between the two sides of the spinal cord. Whereas inhibitory interneurons ensure the coordination of motoneurons controlling antagonistic muscles, excitatory interneurons are believed to represent the core components for the generation of the locomotor rhythm.Determining the identity of the interneurons at the origin of excitation necessary for the normal generation of locomotor activity is central for understanding the principles of organization and function of locomotor circuits. However, the molecular identity of these excitatory interneurons has remained unclear. A prominent class of excitatory interneurons is the V2a interneurons, defined by Chx10 expression and derived from the p2 progenitor domain with homologous counterparts across vertebrate species (21,(25)(26)(27). In larval zebrafish and newborn mice, V2a interneurons have been shown to project to motoneurons and to be recruited in a frequency-dependent manner (28-32). These properties are consistent with the possibility that this class of interneurons represents a source of excitation within the spinal locomotor circuit.In newborn mice, however, genetic elimination of V2a interneurons has been reported to have little effect on the rhythmic output of the locomotor circuits induced by pharmacological means (33, 34). The absence of tangible effects on the excitability of the locomotor circuit in the absence of V2a interneurons led to the conclusion that these interneurons are not essential fo...

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Origin of excitatory drive to a spinal locomotor network

Cited by 55 publications

References 30 publications

Initiation of Locomotion in Adult Zebrafish

Initiation of Locomotion in Adult Zebrafish

Simple cellular and network control principles govern complex patterns of motor behavior

Origin of excitation underlying locomotion in the spinal circuit of zebrafish

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