Dendrites Of Motoneurons Research Articles

Patterning and organization of motor neuron dendrites in the Drosophila larva

Precise patterns of motor neuron connectivity depend on the proper establishment and positioning of the dendritic arbor. However, how different motor neurons orient their dendrites to selectively establish synaptic connectivity is not well understood. The Drosophila neuromuscular system provides a simple model to investigate the underlying organizational principles by which distinct subclasses of motor neurons orient their dendrites within the central neuropil. Here we used genetic mosaic techniques to characterize the diverse dendritic morphologies of individual motor neurons from five main nerve branches (ISN, ISNb, ISNd, SNa, and SNc) in the Drosophila larva. We found that motor neurons from different nerve branches project their dendrites to largely stereotyped mediolateral domains in the dorsal region of the neuropil providing full coverage of the receptive territory. Furthermore, dendrites from different motor neurons overlap extensively, regardless of subclass, suggesting that repulsive dendrite-dendrite interactions between motor neurons do not influence the mediolateral positioning of dendritic fields. The anatomical data in this study provide important information regarding how different subclasses of motor neurons organize their dendrites and establishes a foundation for the investigation of the mechanisms that control synaptic connectivity in the Drosophila motor circuit.

Dendritic targeting in the leg neuropil of Drosophila: the role of midline signalling molecules in generating a myotopic map.

Author SummaryDuring development the axons of sensory neurons generate highly ordered ”sensory maps„ within the nervous system that represent specific qualities of the environment. Much less is known about the anatomical organization and development of motor systems. Here, we show that the leg motoneurons of Drosophila organize their dendrites within the central nervous system in a way that reflects the position of the muscles they innervate. These motoneurons generate a ‘myotopic map’ by targeting the growth of their dendrites (sites of synaptic input) into discrete territories during development. The precise targeting of dendrites along the mediolateral axis is controlled by the signaling molecules Slit and Netrin, which are secreted by midline cells. These proteins act as global guidance cues and exert their effects via distinct signaling pathways using receptors called Roundabout and Frazzled, respectively. Previous studies have shown that Slit also helps to position the termini of axons (sites of synaptic output), independent of their synaptic partners. We suggest that the coordinated targeting of both input and output elements of a neural system into a common space using shared global guidance cues could be a simple way of establishing the specificity of synaptic connections within neural networks.

Midline Signalling Systems Direct the Formation of a Neural Map by Dendritic Targeting in the Drosophila Motor System

Author SummaryHow neural networks governing locomotion are organised is less well understood than those governing sensory systems. In the Drosophila embryo dendrites form the input structures of motorneurons, and are arranged along the anterior-posterior axis in the central nervous system to reflect the distribution of body wall muscles in the periphery. Here we examine how a motorneuron dendritic map develops. We find that motorneurons target their dendrites also to distinct medio-lateral territories. This map appears to be “hard-wired” in that its formation does not require synaptic input or the proper positioning of partner terminals. Instead, dendritic targeting is determined by the responsiveness of individual motorneurons to midline guidance cues, mediated by the Slit receptor Robo and the Netrin receptor Frazzled. These findings complement and mirror similar results by others on the positioning of presynaptic axon terminals, and together they suggest a central role for global guidance cues in generating connectivity by delivering partner terminals independently of one another to common “meeting regions.”

Identification of the neural pathway underlying spontaneous crossed phrenic activity in neonatal rats

Cervical spinal cord hemisection at C2 leads to paralysis of the ipsilateral hemidiaphragm in rats. Respiratory function of the paralyzed hemidiaphragm can be restored by activating a latent respiratory motor pathway in adult rats. This pathway is called the crossed phrenic pathway and the restored activity in the paralyzed hemidiaphragm is referred to as crossed phrenic activity. The latent neural pathway is not latent in neonatal rats as shown by the spontaneous expression of crossed phrenic activity. However, the anatomy of the pathway in neonatal rats is still unknown. In the present study, we hypothesized that the crossed phrenic pathway may be different anatomically in neonatal and adult rats. To delineate this neural pathway in neonates, we injected wheat germ agglutinin conjugated to horseradish peroxidase (WGA–HRP), a retrograde transsynaptic tracer, into the phrenic nerve ipsilateral to hemisection. We also injected cholera toxin subunit B–horseradish peroxidase (BHRP) into the ipsilateral hemidiaphragm following hemisection in other animals to determine if there are midline-crossing phrenic dendrites involved in the crossed phrenic pathway in neonatal rats. The WGA–HRP labeling was observed only in the ipsilateral phrenic nucleus and ipsilateral rostral ventral respiratory group (rVRG) in the postnatal day (P) 2, P7, and P28 hemisected rats. Bilateral labeling of rVRG neurons was shown in P35 rats. The BHRP study showed that many phrenic dendrites cross the midline in P2 neonatal rats at both rostral and caudal parts of the phrenic nucleus. There was a marked reduction of crossing dendrites observed in P7 and P28 animals and no crossing dendrites observed in P35 rats. The present results suggest that the crossed phrenic pathway in neonatal rats involves the parent axons from ipsilateral rVRG premotor neurons that cross at the level of obex as well as decussating axon collaterals that cross over the spinal cord midline to innervate ipsilateral phrenic motoneurons following C2 hemisection. In addition, midline-crossing dendrites of the ipsilateral phrenic motoneurons may also contribute to the crossed phrenic pathway in neonates.

Pre-symptomatic alterations in subcellular βCGRP distribution in motor neurons precede astrogliosis in ALS mice

In our study we investigated the pathology-related expression patterns of the two calcitonin gene-related peptide (CGRP) isoforms in spinal cord motor neurons of SOD1G93A mice, an animal model of the human motor neuron disease, amyotrophic lateral sclerosis (ALS). We found that αCGRP and βCGRP gene expression and αCGRP immunoreactivity remained unaltered throughout disease, and αCGRP gene deficiency had no effect on disease progression. In contrast, βCGRP immunoreactivity appeared at atypical sites in degenerating motor neuron cell bodies, axons, and dendrites already in the early pre-symptomatic disease phase around postnatal day 40. A close association of βCGRP-containing dysmorphic dendritic structures with processes of activated astrocytes, in combination with a selective expression of the CGRP receptor by astrocytes, suggests that βCGRP may function as a motor neuron-derived signaling molecule for astrocyte activation in ALS.

Staircase Currents in Motoneurons: Insight into the Spatial Arrangement of Calcium Channels in the Dendritic Tree

In spinal motoneurons, activation of dendritically located depolarizing conductances can lead to amplification of synaptic inputs and the production of plateau potentials. Immunohistochemical and computational studies have implicated dendritic CaV1.3 channels in this amplification and suggest that CaV1.3 channels in spinal motoneurons may be organized in clusters in the dendritic tree. Our goal was to provide physiological evidence for the presence of multiple discrete clusters of voltage-gated calcium channels in spinal motoneurons and to explore the spatial arrangement of these clusters in the dendritic tree. We recorded voltage-gated calcium currents from spinal motoneurons in slices of mature mouse spinal cords. We demonstrate that single somatic voltage-clamp steps can elicit multiple inward currents with varying delays to onset, resulting in a current with a "staircase"-like appearance. Recordings from cultured dorsal root ganglion cells at different stages of neurite development provide evidence that these currents arise from the unclamped portions of the dendritic tree. Finally, both voltage- and current-clamp data were used to constrain computer models of a motoneuron. The resultant simulations impose two conditions on the spatial distribution of CaV channels in motoneuron dendrites: one of asymmetry relative to the soma and another of spatial separation between clusters of CaV channels. We propose that this compartmentalization would provide motoneurons with the ability to process multiple sources of input in parallel and integrate this processed information to produce appropriate trains of action potentials for the intended motor behavior.

Derivation of cable parameters for a reduced model that retains asymmetric voltage attenuation of reconstructed spinal motor neuron dendrites

Spinal motor neurons have voltage gated ion channels localized in their dendrites that generate plateau potentials. The physical separation of ion channels for spiking from plateau generating channels can result in nonlinear bistable firing patterns. The physical separation and geometry of the dendrites results in asymmetric coupling between dendrites and soma that has not been addressed in reduced models of nonlinear phenomena in motor neurons. We measured voltage attenuation properties of six anatomically reconstructed and type-identified cat spinal motor neurons to characterize asymmetric coupling between the dendrites and soma. We showed that the voltage attenuation at any distance from the soma was direction-dependent and could be described as a function of the input resistance at the soma. An analytical solution for the lumped cable parameters in a two-compartment model was derived based on this finding. This is the first two-compartment modeling approach that directly derived lumped cable parameters from the geometrical and passive electrical properties of anatomically reconstructed neurons.

Human neural stem cell grafts in the spinal cord of SOD1 transgenic rats: Differentiation and structural integration into the segmental motor circuitry

Cell replacement strategies for degenerative and traumatic diseases of the nervous system depend on the functional integration of grafted cells into host neural circuitry, a condition necessary for the propagation of physiological signals and, perhaps, targeting of trophic support to injured neurons. We have recently shown that human neural stem cell (NSC) grafts ameliorate motor neuron disease in SOD1 transgenic rodents. Here we study structural aspects of integration of neuronally differentiated human NSCs in the motor circuitry of SOD1 G93A rats. Human NSCs were grafted into the lumbar protuberance of 8-week-old SOD1 G93A rats; the results were compared to those on control Sprague-Dawley rats. Using pre-embedding immuno-electron microscopy, we found human synaptophysin (+) terminals contacting the perikarya and proximal dendrites of host alpha motor neurons. Synaptophysin (+) terminals had well-formed synaptic vesicles and were associated with membrane specializations primarily in the form of symmetrical synapses. To analyze the anatomy of motor circuits engaging differentiated NSCs, we injected the retrograde transneuronal tracer Bartha-pseudorabies virus (PRV) or the retrograde marker cholera toxin B (CTB) into the gastrocnemius muscle/sciatic nerve of SOD1 rats before disease onset and also into control rats. With this tracing, NSC-derived neurons were labeled with PRV but not CTB, a pattern suggesting that PRV entered NSC-derived neurons via transneuronal transfer from host motor neurons but not via direct transport from the host musculature. Our results indicate an advanced degree of structural integration, via functional synapses, of differentiated human NSCs into the segmental motor circuitry of SOD1-G93A rats.

Hypoglossal motoneurons in newborn mice receive respiratory drive from both sides of the medulla

Respiratory motor output in bilateral cranial nerves is synchronized, but the underlying synchronizing mechanisms are not clear. We used an in vitro slice preparation from newborn mice to investigate the effect of systematic transsections on respiratory activity in bilateral XII nerves. Complete transsection at the midline resulted in desynchronized rhythm with reduced XII burst amplitude and duration. Transsections in the ventral or dorsal 1/3 of the midline did not desynchronize rhythm. However, transsections in the ventral 2/3 of the midline desynchronized rhythm with characteristic amplitude correlations, where large-amplitude XII-bursts on one side was synchronized with small-amplitude XII-burst on the contralateral side. These characteristic amplitude correlations suggest that hypoglossal motoneurons receive respiratory drive from bilateral sources. Retrograde labeling confirmed that commissural fibers from the pre-Bötzinger complex cross in the mid-1/3 of the midline, and that dendrites of hypoglossal motoneurons project into the contralateral XII nucleus. In conclusion, commissural fibers crossing in the mid-1/3 of the midline are required for synchronization of respiratory activity in bilateral XII nerves. Hypoglossal motoneurons receive respiratory drive from both sides of the medulla, possibly mediated by contralaterally projecting dendrites.

Evolution of gustatory reflex systems in the brainstems of fishes

The great number of species of teleosts permits highly specialized forms to evolve to occupy particular niches. This diversity allows for extreme variations in brain structure according to particular sensory or motor adaptations. In the case of the taste system, goldfish (Carassius auratus L., 1758) and some carps have evolved a specialized intraoral food-sorting apparatus along with corresponding specializations of gustatory centers in the brainstem. A comparison of circuitry within the complex vagal lobe of goldfish, and of the simpler gustatory lobes in catfish (Ictalurus punctatus Rafinesque, 1818) shows numerous similarities in organization and neurotransmitters. Double labeling studies using horseradish peroxidase and biotinylated dextran amine in catfish shows a direct projection from the vagal lobe to the motoneurons of nucleus ambiguous which innervate oropharyngeal musculature. Therefore, a three neuron reflex arc connects gustatory input to motor output. In the vagal lobe of goldfish, a similar three neuron arc can be identified: from primary gustatory afferent, to vagal lobe interneuron, thence to dendrites of the vagal motoneurons that innervate the pharyngeal muscles. Therefore, despite large differences in the gross appearance of the vagal gustatory systems in the brains of catfish and goldfish, the essential connectivity and circuitry is similar. This suggests that evolutionary change in the central nervous system largely proceeds by rearrangement and elaboration of existing systems, rather than by addition of new structures or circuits.

Differential contribution of the Na + ‐K + ‐2Cl − cotransporter NKCC1 to chloride handling in rat embryonic dorsal root ganglion neurons and motor neurons

Plasma membrane chloride (Cl(-)) pathways play an important role in neuronal physiology. Here, we investigated the role of NKCC1 cotransporters (a secondary active Cl(-) uptake mechanism) in Cl(-) handling in cultured rat dorsal root ganglion neurons (DRGNs) and motor neurons (MNs) derived from fetal stage embryonic day 14. Gramicidin-perforated patch-clamp recordings revealed that DRGNs accumulate intracellular Cl(-) through a bumetanide- and Na(+)-sensitive mechanism, indicative of the functional expression of NKCC1. Western blotting confirmed the expression of NKCC1 in both DRGNs and MNs, but immunocytochemistry experiments showed a restricted expression in dendrites of MNs, which contrasts with a homogeneous expression in DRGNs. Both MNs and DRGNs could be readily loaded with or depleted of Cl(-) during GABA(A) receptor activation at depolarizing or hyperpolarizing membrane potentials. After loading, the rate of recovery to the resting Cl(-) concentration (i.e., [Cl(-)](i) decrease) was similar in both cell types and was unaffected by lowering the extracellular Na(+) concentration. In contrast, the recovery on depletion (i.e., [Cl(-)](i) increase) was significantly faster in DRGNs in control conditions but not in low extracellular Na(+). The experimental observations could be reproduced by a mathematical model for intracellular Cl(-) kinetics, in which DRGNs show higher NKCC1 activity and smaller Cl(-)-handling volume than MNs. On the basis of these results, we conclude that embryonic DRGNs show a higher somatic functional expression of NKCC1 than embryonic MNs. The high NKCC1 activity in DRGNs is important for maintaining high [Cl(-)](i), whereas lower NKCC1 activity in MNs allows large [Cl(-)](i) variations during neuronal activity.

V3 Spinal Neurons Establish a Robust and Balanced Locomotor Rhythm during Walking

A robust and well-organized rhythm is a key feature of many neuronal networks, including those that regulate essential behaviors such as circadian rhythmogenesis, breathing, and locomotion. Here we show that excitatory V3-derived neurons are necessary for a robust and organized locomotor rhythm during walking. When V3-mediated neurotransmission is selectively blocked by the expression of the tetanus toxin light chain subunit (TeNT), the regularity and robustness of the locomotor rhythm is severely perturbed. A similar degeneration in the locomotor rhythm occurs when the excitability of V3-derived neurons is reduced acutely by ligand-induced activation of the allatostatin receptor. The V3-derived neurons additionally function to balance the locomotor output between both halves of the spinal cord, thereby ensuring a symmetrical pattern of locomotor activity during walking. We propose that the V3 neurons establish a regular and balanced motor rhythm by distributing excitatory drive between both halves of the spinal cord.

Role of GluR1 in Activity-Dependent Motor System Development

Activity-dependent specification of neuronal architecture during early postnatal life is essential for refining the precision of communication between neurons. In the spinal cord under normal circumstances, the AMPA receptor subunit GluR1 is expressed at high levels by motor neurons and surrounding interneurons during this critical developmental period, although the role it plays in circuit formation and locomotor behavior is unknown. Here, we show that GluR1 promotes dendrite growth in a non-cell-autonomous manner in vitro and in vivo. The mal-development of motor neuron dendrites is associated with changes in the pattern of interneuronal connectivity within the segmental spinal cord and defects in strength and endurance. Transgenic expression of GluR1 in adult motor neurons leads to dendrite remodeling and supernormal locomotor function. GluR1 expression by neurons within the segmental spinal cord plays an essential role in formation of the neural network that underlies normal motor behavior.

The Effects of Aging on Hypoglossal Motoneurons in Rats

Aging can result in a loss of neuronal cell bodies and a decrease in neuronal size in some regions of the brain and spinal cord. Motoneuron loss in the spinal cord is thought to contribute to the progressive decline in muscle mass and strength that occurs with age (sarcopenia). Swallowing disorders represent a large clinical problem in elderly persons; however, age-related alterations in cranial motoneurons that innervate muscles involved in swallowing have been understudied. We aimed to determine if age-related alterations occurred in the hypoglossal nucleus in the brainstem. If present, these changes might help explain alterations at the neuromuscular junction and changes in the contractile properties of tongue muscle that have been reported in older rats. We hypothesized that with increasing age there would be a loss of motoneurons and a reduction in neuronal size and the number of primary dendrites associated with each hypoglossal motoneuron. Neurons in the hypoglossal nucleus were visualized with the neuronal marker NeuN in young (9-10 months), middle-aged (24-25 months), and old (32-33 months) male F344/BN rats. Hypoglossal motoneurons were retrograde-labeled with injections of Cholera Toxin beta into the genioglossus muscle of the tongue and visualized using immunocytochemistry. Results indicated that the number of primary dendrites of hypoglossal motoneurons decreased significantly with age, while no age-associated changes were found in the number or size of hypoglossal motoneurons. Loss of primary dendrites could reduce the number of synaptic inputs and thereby impair function.

Modest alterations in patterns of motor neuron dendrite morphology in the Fmr1 knockout mouse model for fragile X

Fragile X, an inheritable form of mental retardation, is caused by the inactivation of a gene on the X chromosome, FMR1 which codes for an RNA binding protein, fragile X mental retardation protein. Loss of this protein is associated with reduced complexities of neuronal dendrites and alterations in spine morphology in a number of cortical brain regions, and these deficits may underlie the cognitive impairment observed in fragile X patients. Among the many symptoms of fragile X are altered motor functions, although the neuronal basis for these remains unclear. In this study we investigated whether knockout of Fmr1 in the mouse model of fragile X altered dendrite morphology in developing spinal cord motor neurons. We find that Fmr1 knockout leads to modest alterations in the distribution of dendritic arbor across the span of the motor neuron dendritic tree in 2- and 4-week-old mice, compared to wild-type controls, consistent with slower rates of extension and abnormal pruning of intermediate dendritic segments. These studies suggest that some motor deficits in fragile X patients may be due to abnormal maturation of dendritic patterning within spinal motor neurons, and suggest that strategies aimed at preventing motor impairment in fragile X patients may be targeted at motor functions during early development.

An In Vitro Protocol for Recording From Spinal Motoneurons of Adult Rats

In vitro slice preparations of CNS tissue are invaluable for studying neuronal function. However, up to now, slice protocols for adult mammal spinal motoneurons--the final common pathway for motor behaviors--have been available for only limited portions of the spinal cord. In most cases, these preparations have not been productive due to the poor viability of motoneurons in vitro. This report describes and validates a new slice protocol that for the first time provides reliable intracellular recordings from lumbar motoneurons of adult rats. The key features of this protocol are: preexposure to 100% oxygen; laminectomy prior to perfusion; anesthesia with ketamine/xylazine; embedding the spinal cord in agar prior to slicing; and, most important, brief incubation of spinal cord slices in a 30% solution of polyethylene glycol to promote resealing of the many motoneuron dendrites cut during sectioning. Together, these new features produce successful recordings in 76% of the experiments and an average action potential amplitude of 76 mV. Motoneuron properties measured in this new slice preparation (i.e., voltage and current thresholds for action potential initiation, input resistance, afterhyperpolarization size and duration, and onset and offset firing rates during current ramps) are comparable to those recorded in vivo. Given the mechanical stability and precise control over the extracellular environment afforded by an in vitro preparation, this new protocol can greatly facilitate electrophysiological and pharmacological study of these uniquely important neurons and other delicate neuronal populations in adult mammals.

Expression of the N-methyl- d-aspartate receptor subunit NR3B regulates dendrite morphogenesis in spinal motor neurons

During postnatal development, the dendrites of spinal motor neurons are refined in an activity-dependent manner that can be influenced by blocking activation of N-methyl- d-aspartate (NMDA) receptors. In late postnatal life, dendritic refinement ceases, and dendrite architecture is unaffected by NMDA antagonists; however the molecular substrate for limiting dendritic plasticity is not understood. During late postnatal development, expression of the NR3B NMDA receptor subunit, a putative dominant-negative subunit that reduces glutamate-induced ionic currents, is upregulated within motor neurons. To investigate whether increasing NR3B expression may contribute to the loss in late development of activity-dependent dendritic reorganization in the spinal cord, we over-expressed NR3B in cultured rat spinal motor neurons, and compared its effects on dendrite morphology with the effects of pharmacological blockade of NMDA receptors. We found that over-expression of the NR3B receptor subunit increased the length and complexity of dendritic arbor, and increased numbers of dendritic filopodia, suggesting that NR3B promotes the addition of branch segments in developing motor neurons. In contrast, blockade of NMDA receptor activity by the NMDA antagonist dl-2-amino-5-phosphonovalerate (AP5) had little effect on the overall length or complexity of dendritic arbor. Instead, treatment with AP5 resulted in significant reorganization of dendritic arbor in a manner that favored addition of dendritic segments of high branch orders, at the expense of those closer to the cell body. These results suggest that expression of the NR3B subunit may participate in activity-dependent reorganization of dendritic architecture, but via a mechanism that may be inconsistent with loss of NMDA receptor activity.

Movement‐related receptive fields of spinal motoneurones with active dendrites

The primary control of spinal motoneurone excitability is mediated by descending monoaminergic systems, which have diffuse effects on multiple motor pools. Much of the sensory input evoked by movement is also distributed broadly to multiple joints. The muscle spindle Ia afferent system, however, is sharply focused, with Ia excitation restricted to close synergists and Ia reciprocal inhibition only shared between antagonists acting at a single joint. We studied the interaction of neuromodulatory and sensory inputs in determining the movement-related receptive field (MRRF) of motoneurones during passive joint movements of the cat hindlimb. In a decerebrate preparation with tonic monoaminergic input to the cord, the MRRFs tended to be focused for the ankle and knee extensor motor pools studied. Ankle rotation produced larger synaptic currents in ankle extensors than knee or hip rotations and knee rotation dominated input to the knee extensors. The persistent inward current (PIC) in motoneurone dendrites, which is facilitated by monoaminergic input, amplified the MRRF about 2-fold, consistent with its effects on other inputs. Acute spinal transaction markedly broadened MRRFs, with hip rotation generating large currents in both ankle and knee extensors. Spinalization also eliminated amplification of MRRFs, as expected from elimination of descending monoaminergic input. Ia reciprocal inhibition is very effective in suppressing dendritic PICs and thus provides a local and specific PIC control system to oppose the diffuse PIC facilitation from descending monoaminergic systems. The focused MRRF seen in the intact cord state would allow reciprocal inhibition to fulfil this role without undue interference from multijoint input from other afferent systems.

The control of motoneurone activity: getting all of the players on the same stage

Studies of motor control, particularly at the level of the spinal cord, have placed a high premium on the exact pathways used by segmental and descending signals en route to motoneurones. The perceived importance of the role of these pathways has inspired numerous studies that have firmly embedded the term ‘identified interneuron’ into the lexicon of spinal neuroscience (Jankowska, 2001). While not disputing the need for a precise description of the circuits linking spinal neurons, to attain a truly comprehensive understanding of the control of motor activity by these circuits requires an equally precise description of the type of sensory information that is transmitted by these circuits and the transformation of this information by the intrinsic properties of spinal neurons, especially motoneurones. Thus, the control of motoneurone activity is similar to a theatrical production in which many actors and actresses, in this case representing different circuits, types of sensory information, and intrinsic properties, occupy the same stage and engage in an interactive dialogue. When viewed from the perspective of a scientist, the challenge is to get all of these players on the same experimental stage. Electrical stimulation of peripheral nerves is a time-honoured means of defining the source and type of information delivered by muscle, joint and cutaneous afferents (Matthews, 1972). When used in conjunction with electrophysiological recordings that are synchronized to the time of the stimulus delivery, electrical stimulation of peripheral nerves offers a powerful tool to discriminate the neuronal circuits responsible for the transmission of information arising from individual classes of sensory afferents. However, this technique is ill-suited to mimic the sensory information that is generated by natural movements of the limb. Under these conditions, afferents from multiple locations and modalities will be activated together and the activity in each afferent will vary depending on the position of the limb and the kinematics of the limb movement. Thus, in the context of the desired experimental play, electrical stimulation artificially limits the number of the players that represent the sum of sensory information generated by natural movements and the multiplicity of pathways engaged in the transmission of this information. In this issue of The Journal of Physiology, Hyngstrom et al. (2008) take advantage of robotic technology to get many of the key players on the same experimental stage. In this instance, a robot was used to independently rotate the ankle, knee and hip, or all three joints at the same time. These movements generate a multimodal barrage of sensory signals that arise from sensory receptors located throughout the hindlimb. A small number of investigators have previously used robots to examine the sensory responses of ascending tract neurons in the spinal cord (e.g. Bosco et al. 1996). However, Hyngstrom and colleagues have applied this technology in a way that allows us to listen to the dialogue between the many players representing sensory information, circuits, and importantly, the intrinsic properties of motoneurones. The dendrites of motoneurones possess an array of intrinsic conductances, including a set of voltage-dependent sodium and calcium channels that generate persistent inward currents (PICs, Heckman et al. 2003). PICs are readily activated or deactivated by sensory stimuli in decerebrate animals due to the actions of monoamines released by descending pathways. However, in the acute period following spinal transection, modulation of PICs by segmental circuits is greatly diminished. Thus, by comparing the current reaching the soma of ankle or knee extensor motoneurones in decerebrate and acutely spinalized animals during robotically controlled limb movements, Hyngstrom and colleagues were able to isolate the role of PICs (i.e. one of the intrinsic property players) during activation of multiple spinal circuits by physiologically relevant sensory information (represented by several players). The results of the study are described in the form of movement related receptive fields. These fields are defined by the strength of the signals received from different joints. The data suggest that PICs reduce the dimensions of movement related receptive fields. For example, in the absence of PIC modulation by descending monoaminergic systems, rotations at the hip generate large synaptic currents in ankle extensor motoneurones. These currents are greatly reduced in the presence of PIC modulation. It is perhaps ironic, given the original goal of recruiting more key players to the stage, that the interaction between these players causes some of the new members of the cast to lose their voices. This outcome may indicate that the players representing descending monoaminergic systems and PICs are the stars in this play. It is tempting to speculate that the more potent actions of intraspinal monoaminergic systems in chronic models of spinal cord injury may raise the voices of excitatory muscle afferent circuits and thereby contribute to muscle spasms (Harvey et al. 2006). However, the words for this play have yet to be written.

Active properties of motoneurone dendrites: diffuse descending neuromodulation, focused local inhibition

The dendrites of spinal motoneurones are highly active, generating a strong persistent inward current (PIC) that has an enormous impact on processing of synaptic input. The PIC is subject to regulation by descending neuromodulatory systems releasing the monoamines serotonin and noradrenaline. At high monoaminergic drive levels, the PIC dominates synaptic integration, generating an intrinsic dendritic current that is as much as 5-fold larger than the current entering via synapses. Without the PIC, motoneurone excitability is very low. Presumably, this descending control of the synaptic integration via the PIC is used to adjust the excitability (gain) of motoneurones for different motor tasks. A problem with this gain control is that monoaminergic input to the cord is very diffuse, affecting many motor pools simultaneously, probably including both agonists and antagonists. The PIC is, however, exquisitely sensitive to the reciprocal inhibition mediated by length sensitive muscle spindle Ia afferents and Ia interneurones. Reciprocal inhibition is tightly focused, shared only between strict mechanical antagonists, and thus can act to 'sculpt' specific movement patterns out of a background of diffuse neuromodulation. Thus it is likely that motoneurone gain is set by the interaction between diffuse descending neuromodulation and specific and focused local synaptic inhibitory circuits.