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S Grillner

Publications and source records attributed to S Grillner.

At least 19 recordsLinked to original sources
PubMed2003

Postural control in the rabbit maintaining balance on the tilting platform.

A deviation from the dorsal-side-up body posture in quadrupeds activates the mechanisms for postural corrections. Operation of these mechanisms was studied in the rabbit maintaining balance on a platform periodically tilted in the frontal plane. First, we characterized the kinematics and electromyographic (EMG) patterns of postural responses to tilts. It was found that a reaction to tilt includes an extension of the limbs on the side moving down and flexion on the opposite side. These limb movements are primarily due to a modulation of the activity of extensor muscles. Second, it was found that rabbits can effectively maintain the dorsal-side-up body posture when complex postural stimuli are applied, i.e., asynchronous tilts of the platforms supporting the anterior and posterior parts of the body. These data suggest that the nervous mechanisms controlling positions of these parts of the body can operate independently of each other. Third, we found that normally the somatosensory input plays a predominant role for the generation of postural responses. However, when the postural response appears insufficient to maintain balance, the vestibular input contributes considerably to activation of postural mechanisms. We also found that an asymmetry in the tonic vestibular input, caused by galvanic stimulation of the labyrinths, can affect the stabilized body orientation while the magnitude of postural responses to tilts remains unchanged. Fourth, we found that the mechanisms for postural corrections respond only to tilts that exceed a certain (threshold) value.

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PubMed2003

Comparison of the motor effects of individual vestibulo- and reticulospinal neurons on dorsal and ventral myotomes in lamprey.

In the lamprey (a lower vertebrate), motor commands from the brain to the spinal cord are transmitted through the reticulospinal (RS) and vestibulospinal (VS) pathways. The axons of larger RS neurons reach the most caudal of approximately 100 spinal segments, whereas the VS pathway does not descend below the 15th segment. This study was carried out to compare functional projections of RS and VS neurons in the rostral spinal segments that the neurons innervate together. To reveal these projections, individual RS or VS neurons were stimulated, and the responses of different groups of spinal motoneurons were recorded in ventral root branches to dorsal and ventral parts of myotomes. The responses were detected using a spike-triggered averaging technique on the background of ongoing motoneuronal activity. Individual RS and VS neurons exerted uniform effects on segmental motor output within this rostral part of the spinal cord. The effects of VS neurons on different groups of motoneurons were weaker and less diverse than those of RS neurons. The results indicate that VS neurons are able to elicit a flexion of the rostral part of the body and to turn the head in different planes without affecting more caudal parts. By contrast, larger RS neurons can elicit head movement only together with movement of a considerable part of the body and thus seem to be responsible for formation of gross motor synergies.

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PubMed2001

Heterogeneity of the population of command neurons in the lamprey.

The effects of signals transmitted from the brain to the spinal locomotor networks by a population of command neurons are determined by specific functional projections of each individual neuron. To reveal these projections, we used a simple vertebrate model, the lamprey, in which responses of the spinal networks to spikes in single reticulospinal axons were detected by using the spike-triggered averaging of the motoneuronal activity. We found that individual neurons exert a uniform effect on the segmental motor output along the whole extent of their axons. Twenty different patterns of effect, that is, combinations of influences on the segmental motoneuron pools, were found. The widespread projections and heterogeneity of the population of command neurons present a basis for formation of different gross motor synergies.

Action Potentials↗
PubMed2001

Gating and braking of short- and long-term modulatory effects by interactions between colocalized neuromodulators.

Spinal locomotor networks in the lamprey are modulated by tachykinin neuropeptides. A single 10 min application of the tachykinin substance P evokes a short-term ( approximately 1 hr) presynaptic facilitation of glutamate release and the postsynaptic potentiation of NMDA responses. The latter effect induces a long-term (>24 hr) protein synthesis-dependent increase in the frequency of network activity. Tachykinins are contained in a ventromedial spinal plexus into which the medial dendrites of network neurons project. Neurons in this plexus also contain colocalized dopamine and 5-HT. Here, dynamic plasticity evoked by modulator interactions has been examined by investigating the effects of 5-HT and dopamine on specific cellular, synaptic, and network effects of substance P. Preapplied 5-HT blocked the substance P-mediated increase in the network burst frequency and the potentiation of NMDA-evoked cellular responses that underlies its induction. 5-HT also blocked the presynaptic facilitation of glutamatergic synaptic transmission by substance P. The presynaptic, but not postsynaptic, effect of 5-HT was reduced by the protein phosphatase 2B inhibitor cypermethrin. Dopamine did not directly modulate the effects of substance P. However, it reduced the presynaptic interactive effect of 5-HT and thus gated the presynaptic potentiation of glutamatergic inputs by substance P. However, the substance P-mediated potentiation of NMDA responses was not gated by dopamine, and thus the long-term network modulation was not induced. Neuromodulator effects and their interactions can thus be modulated. By selecting components from the modulatory repertoire of substance P, these interactions evoke dynamic changes in short- and long-term synaptic and network plasticity.

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PubMed2001

Ion channels of importance for the locomotor pattern generation in the lamprey brainstem-spinal cord.

The intrinsic function of the spinal network that generates locomotion can be studied in the isolated brainstem-spinal cord of the lamprey, a lower vertebrate. The motor pattern underlying locomotion can be elicited in the isolated spinal cord. The network consists of excitatory glutamatergic and inhibitory glycinergic interneurones with known connectivity. The current review addresses the different subtypes of ion channels that are present in the cell types that constitute the network. In particular the roles of the different subtypes of Ca2+ channels and potassium channels that regulate integrated neuronal functions, like frequency regulation, spike frequency adaptation and properties that are important for generating features of the motor pattern (e.g. burst termination), are reviewed. By knowing the role of an ion channel at the cellular level, we also, based on previous knowledge of network connectivity, can understand which effect a given ion channel may exert at the different levels from molecule and cell to network and behaviour.

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PubMed2001

Modeling postural control in the lamprey.

A phenomenological model of the mechanism of stabilization of the body orientation during locomotion (dorsal side up) in the lamprey is presented. The mathematical modeling is based on experimental results obtained during investigations of postural control in lampreys using a combined in vivo and robotics approach. The dynamics of the model agree qualitatively with the experimental data. It is shown by computer simulations that postural correction commands from reticulospinal neurons provide information sufficient to stabilize body orientation in the lamprey. The model is based on differences between the effects exerted by the vestibular apparatus on the left and the right side.

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PubMed2001

Slow dorsal-ventral rhythm generator in the lamprey spinal cord.

In the isolated lamprey spinal cord, a very slow rhythm (0.03-0.11 Hz), superimposed on fast N-methyl-D-aspartate (NMDA)-induced locomotor activity (0.26-2.98 Hz), could be induced by a blockade of GABA(A) or glycine receptors or by administration of (1 s, 3 s)-l-aminocyclopentane-1,3-dicarboxylic acid a metabotropic glutamate receptor agonist. Ventral root branches supplying dorsal and ventral myotomes were exposed bilaterally to study the motor pattern in detail. The slow rhythm was expressed in two main forms: 1) a dorsal-ventral reciprocal pattern was the most common (18 of 24 preparations), in which bilateral dorsal branches were synchronous and alternated with the ventral branches, in two additional cases a diagonal dorsal-ventral reciprocal pattern with alternation between the left (or right) dorsal and the right (or left) ventral branches was observed; 2) synchronous bursting in all branches was encountered in four cases. In contrast, the fast locomotor rhythm occurred always in a left-right reciprocal pattern. Thus when the slow rhythm appeared in a dorsal-ventral reciprocal pattern, fast rhythms would simultaneously display left-right alternation. A longitudinal midline section of the spinal cord during ongoing slow bursting abolished the reciprocal pattern between ipsilateral dorsal and ventral branches but a synchronous burst activity could still remain. The fast swimming rhythm did not recover after the midline section. These results suggest that in addition to the network generating the swimming rhythm in the lamprey spinal cord, there is also a network providing slow reciprocal alternation between dorsal and ventral parts of the myotome. During steering, a selective activation of dorsal and ventral myotomes is required and the neural network generating the slow rhythm may represent activity in the spinal machinery used for steering.

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PubMed2001

Lateral turns in the Lamprey. II. Activity of reticulospinal neurons during the generation of fictive turns.

We studied the neural correlates of turning movements during fictive locomotion in a lamprey in vitro brain-spinal cord preparation. Electrical stimulation of the skin on one side of the head was used to evoke fictive turns. Intracellular recordings were performed from reticulospinal cells in the middle (MRRN) and posterior (PRRN) rhombencephalic reticular nuclei, and from Mauthner cells, to characterize the pattern of activity in these cell groups, and their possible functional role for the generation of turns. All recorded reticulospinal neurons modified their activity during turns. Many cells in both the rostral and the caudal MRRN, and Mauthner cells, were strongly excited during turning. The level of activity of cells in rostral PRRN was lower, while the lowest degree of activation was found in cells in caudal PRRN, suggesting that MRRN may play a more important role for the generation of turning behavior. The sign of the response (i.e., excitation or inhibition) to skin stimulation of a neuron during turns toward (ipsilateral), or away from (contralateral) the side of the cell body was always the same. The cells could thus be divided into four types: 1) cells that were excited during ipsilateral turns and inhibited during contralateral turns; these cells provide an asymmetric excitatory bias to spinal networks and presumably play an important role for the generation of turns; these cells were common (n = 35; 52%) in both MRRN and PRRN; 2) cells that were excited during turns in either direction; these cells were common (n = 19; 28%), in particular in MRRN; they could be involved in a general activation of the locomotor system after skin stimulation; some of the cells were also more activated during turns in one direction and could contribute to an asymmetric turn command; 3) one cell that was inhibited during ipsilateral turns and excited during contralateral turns; and 4) cells (n = 12; 18%) that were inhibited during turns in either direction. In summary, our results show that, in the lamprey, the large majority of reticulospinal cells have responses during lateral turns that are indicative of a causal role for these cells in turn generation. This also suggests a considerable overlap between the command system for lateral turns evoked by skin stimulation, which was studied here, and other reticulospinal command systems, e.g., for lateral turns evoked by other types of stimuli, initiation of locomotion, and turns in the vertical planes.

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PubMed2000

The intrinsic function of a motor system--from ion channels to networks and behavior.

The forebrain, brainstem and spinal cord contribution to the control of locomotion is reviewed in this article. The lamprey is used as an experimental model since it allows a detailed cellular analysis of the neuronal network underlying locomotion. The focus is on cellular mechanisms that are important for the pattern generation, as well as different types of pre- and postsynaptic modulation. This experimental model is bridging the gap between the molecular and cellular level to the network and behavioral level.

Animals↗
PubMed2000

From egg to action.

The development of the neural control circuitry underlying different patterns of behavior is rapidly expanding area of interest in neuroscience. New important insights have been gained over the last few years at different molecular, cellular, network, and behavioral levels. Based primarily on the issues presented in the review articles in this issue, I have added some reflections as to what I find most challenging and important.

Animals↗
PubMed2000

The spinal 5-HT system contributes to the generation of fictive locomotion in lamprey.

Activation of NMDA receptors evokes sustained fictive locomotion in the isolated spinal cord of the sea lamprey Petromyzon marinus (P. marinus), but in the river lamprey Lampetra fluviatilis (L. fluviatilis) the ventral root activity is often irregular. A previous study showed that the number of 5-HT immunoreactive fibres, neurones and varicosities are much lower in the spinal cord of L. fluviatilis than in P. marinus. To further analyse the underlying mechanisms, the present study investigated the role of the 5-HT system in stabilising fictive locomotion. In P. marinus a blockade of 5-HT1A receptors by spiperone reversibly increased the frequency and the coefficient of variation. This implies that there is an endogenous release of 5-HT during fictive locomotion that is important for the generation of locomotor activity. In L. fluviatilis bath applied NMDA or D-glutamate evoked in most cases irregular activity. An addition of 5-HT (0.5-2 microM) rapidly stabilised the burst generation and led to a sustained fictive locomotion. In a split-bath configuration, NMDA administered to the rostral part of the spinal cord in P. marinus evoked fictive locomotion in both the rostral part and the first few segments of the caudal part. When spiperone was added to the caudal part, the burst activity changed into tonic activity within 10 min. Taken together, these results indicate that activity in the intrinsic 5-HT system in the lamprey spinal locomotor network contributes significantly to the rhythm generation. The quantitative differences with regard to the 5-HT plexus between P. marinus and L. fluviatilis may account for the observed discrepancy between the two species.

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PubMed2000

GABA(B)-ergic modulation of burst rate and intersegmental coordination in lamprey: experiments and simulations.

Neuromodulators which influence the operation of neural networks act as a rule via several cellular and synaptic mechanisms. Activation of GABA(B)-receptors in the lamprey spinal cord reduce both calcium currents and the peak amplitude of the post-spike afterhyperpolarization (AHP). Activation of GABA(B)-receptors reduce the segmental alternation rate and modifies the intersegmental coordination when the spinal locomotor circuits are activated by NMDA. Using physiological experiments we find that a reduced AHP is not sufficient to account for the observed reduction of the burst rate. Computer simulations revealed that either a reduced AHP or calcium current could alter the phase coordination between the segments similar to earlier experiments.

Action Potentials↗
PubMed2000

Crossed reciprocal inhibition evoked by electrical stimulation of the lamprey spinal cord.

Activation of a motoneuron pool is often accompanied by inhibition of the antagonistic pool through a system of reciprocal inhibition between the two parts of the neuronal network controlling the antagonistic pools. In the present study, we describe the activity of such a system in the isolated spinal cord of the lamprey, when a tonic motor output is evoked by extracellular stimulation (0.5-1 s train of pulses, 20 Hz) of either end of the spinal cord. With two electrodes symmetrically positioned in relation to the midline, stimulation with either of them separately elicited prolonged (1-5 s) ipsilateral ventral root activity. Activity could be abolished by stronger, simultaneously applied, stimulation of the contralateral side of the cord, suggesting that reciprocal inhibition between hemisegments operates when a tonic motor output is generated. Simultaneous stimulation of both sides of the spinal cord with a single electrode with a large tip (300-400 microm in diameter), positioned over the anatomical midline, elicited inconsistent right-side, leftside, or bilateral ventral root responses. A minor displacement (10-20 microm) to the left or right from the midline resulted in activation of ipsilateral motoneurons, whereas the contralateral motoneurons were silent. These findings indicate that a small asymmetry in the excitatory drive to the left and right spinal hemisegments can be further amplified by reciprocal inhibition between the hemisegments. Longitudinal splitting of the spinal cord along the midline resulted in reduced reciprocal inhibition between the hemisegments separated by the lesion. The reduction was proportional to the extent of the split. The inhibition was abolished when the split reached nine segments in length. From these experiments, the longitudinal distribution of the commissural axons responsible for inhibition of contralateral motor output could be estimated.

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PubMed2000

The activity-dependent plasticity of segmental and intersegmental synaptic connections in the lamprey spinal cord.

Activity-dependent synaptic plasticity has been proposed as a contributory factor in the patterning of rhythmic network activity. However, its role has not been examined in detail. Here, paired or triple intracellular recordings have been made from identified neurons in the lamprey locomotor network to examine the potential relevance of activity-dependent synaptic plasticity in segmental and intersegmental spinal networks. Segmental inputs from glutamatergic excitatory interneurons (EIN) to ipsilateral glycinergic crossed caudal (CC) interneurons were facilitated or depressed during spike trains at 5-20 Hz. Connections between EINs were depressed. Glycinergic inputs from small ipsilateral inhibitory interneurons were depressed in motor neurons, but were facilitated in CC interneurons. Excitatory inputs from small crossing interneurons to motor neurons were depressed, whereas inhibitory inputs were unaffected. With the exception of connections between EINs, significant effects occurred with stimulation that mimicked interneuron spiking during network activity. Intersegmental EIN synaptic properties were also investigated. EIN inputs did not differ significantly when examined from zero to four segments rostral to motor neurons or CC interneurons. However, caudally located EINs evoked greater activity-dependent facilitation than did rostral EINs. Whilst the amplitude or plasticity of EIN inputs in the rostral or mid-trunk regions of the spinal cord did not differ, EINs in the caudal trunk region evoked greater facilitation. Synaptic transmission between locomotor network neurons thus exhibits activity-dependent plasticity in response to physiologically relevant stimulation. Activity-dependent plasticity could thus contribute to the patterning of the rhythmic network output.

Action Potentials↗
PubMed2000

Activity of reticulospinal neurons during locomotion in the freely behaving lamprey.

The reticulospinal (RS) system is the main descending system transmitting commands from the brain to the spinal cord in the lamprey. It is responsible for initiation of locomotion, steering, and equilibrium control. In the present study, we characterize the commands that are sent by the brain to the spinal cord in intact animals via the reticulospinal pathways during locomotion. We have developed a method for recording the activity of larger RS axons in the spinal cord in freely behaving lampreys by means of chronically implanted macroelectrodes. In this paper, the mass activity in the right and left RS pathways is described and the correlations of this activity with different aspects of locomotion are discussed. In quiescent animals, the RS neurons had a low level of activity. A mild activation of RS neurons occurred in response to different sensory stimuli. Unilateral eye illumination evoked activation of the ipsilateral RS neurons. Unilateral illumination of the tail dermal photoreceptors evoked bilateral activation of RS neurons. Water vibration also evoked bilateral activation of RS neurons. Roll tilt evoked activation of the contralateral RS neurons. With longer or more intense sensory stimulation of any modality and laterality, a sharp, massive bilateral activation of the RS system occurred, and the animal started to swim. This high activity of RS neurons and swimming could last for many seconds after termination of the stimulus. There was a positive correlation between the level of activity of RS system and the intensity of locomotion. An asymmetry in the mass activity on the left and right sides occurred during lateral turns with a 30% prevalence (on average) for the ipsilateral side. Rhythmic modulation of the activity in RS pathways, related to the locomotor cycle, often was observed, with its peak coinciding with the electromyographic (EMG) burst in the ipsilateral rostral myotomes. The pattern of vestibular response of RS neurons observed in the quiescent state, that is, activation with contralateral roll tilt, was preserved during locomotion. In addition, an inhibition of their activity with ipsilateral tilt was clearly seen. In the cases when the activity of individual neurons could be traced during swimming, it was found that rhythmic modulation of their firing rate was superimposed on their tonic firing or on their vestibular responses. In conclusion, different aspects of locomotor activity-initiation and termination, vigor of locomotion, steering and equilibrium control-are well reflected in the mass activity of the larger RS neurons.

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PubMed2000

Roles of high-voltage-activated calcium channel subtypes in a vertebrate spinal locomotor network.

Lamprey spinal cord neurons possess N-, L-, and P/Q-type high-voltage-activated (HVA) calcium channels. We have analyzed the role of the different HVA calcium channels subtypes in the overall functioning of the spinal locomotor network by monitoring the influence of their specific agonists and antagonists on synaptic transmission and on N-methyl-D-aspartate (NMDA)-elicited fictive locomotion. The N-type calcium channel blocker omega-conotoxin GVIA (omega-CgTx) depressed synaptic transmission from excitatory and inhibitory interneurons. Blocking L-type and P/Q-type calcium channels with nimodipine and omega-agatoxin, respectively, did not affect synaptic transmission. Application of omega-CgTx initially decreased the frequency of the locomotor rhythm, increased the burst duration, and subsequently increased the coefficient of variation and disrupted the motor pattern. These effects were accompanied by a depression of the synaptic drive between neurons in the locomotor network. Blockade of L-type channels by nimodipine also decreased the frequency and increased the duration of the locomotor bursts. Conversely, potentiation of L-type channels increased the frequency of the locomotor activity and decreased the duration of the ventral root bursts. In contrast to blockade of N-type channels, blockade or potentiation of L-type calcium channels had no effect on the stability of the locomotor pattern. The P/Q-type calcium channel blocker omega-agatoxin IVA had little effect on the locomotor frequency or burst duration. The results indicate that rhythm generation in the spinal locomotor network of the lamprey relies on calcium influx through L-type and N-type calcium channels.

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