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S Grillner

Publications and source records attributed to S Grillner.

At least 127 records · Page 7Linked to original sources
PubMed1992

A computer-based model for realistic simulations of neural networks. II. The segmental network generating locomotor rhythmicity in the lamprey.

1. To analyze the function of the spinal interneuronal network generating locomotion in the lamprey CNS, a vertebrate model system, we performed computer simulations with realistic model neurons possessing the essential properties of their biological counterparts. 2. The segmental network has been simulated by modeling experimentally established types of neurons with their specific membrane properties and synaptic interconnections. Fictive locomotor activity, which can be experimentally induced by elevating the background excitability by bath application of excitatory amino acids, was simulated by opening membrane conductances for kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptors. Kainate/AMPA receptor activation induced a rhythm in the middle and upper part of the physiological burst frequency range, whereas NMDA receptor activation evoked bursting in the lower part of the range, which corresponds well to earlier experimental findings. 3. Several factors contributing to the termination of the burst were studied and their interaction was assessed in simulations of the network. 1) The summation of spike afterhyperpolarizations (late AHPs), leading to adaptation of the discharge, acts as a primary burst-terminating factor at lower rates of kainate/AMPA-induced bursting, and it also interacts with the NMDA-induced oscillatory membrane properties during slow rhythmicity. 2) The termination of the depolarized NMDA plateau is another important factor during NMDA-evoked rhythmicity. 3) The synaptic inhibition from lateral interneurons to the interneurons mediating reciprocal inhibition is important at higher rates of kainate/AMPA-induced bursting. 4. The mechanism of action of 5-hydroxytryptamine (5-HT) on the lamprey segmental network was further investigated by simulation. 5-HT is known to lower the burst frequency during fictive locomotion and also to decrease the conductance through the Ca(2+)-dependent K+ channels, and thereby the size of the late AHP that follows the action potential. Decreasing this conductance in the network simulations resulted in a lesser amount of AHP summation and thereby less frequency adaptation during the burst, longer bursts, and a lower locomotor frequency. Thus the selective action of 5-HT on the Ca(2+)-dependent K+ channels, and hence on the AHP, can account for the modulatory effect on the fictive locomotor rhythm seen experimentally. 5. The results demonstrate that the present simulation of the segmental network can account for essential features of the motor pattern seen experimentally during lamprey locomotion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Co-localized GABA and somatostatin use different ionic mechanisms to hyperpolarize target neurons in the lamprey spinal cord.

gamma-Aminobutyric acid (GABA) and somatostatin are co-localized in cells close to the central canal in the lamprey. These cells project to the lateral margin of the spinal cord where they form a GABA and somatostatin containing plexus. Stretch receptor neurons (edge cells) are situated along the lateral margin of the spinal cord and their dendrites extend into the GABA and somatostatin containing plexus. To investigate whether GABA and/or somatostatin exert an affect on edge cells, these putative transmitters were applied from extracellular pipettes onto edge cells during intracellular recordings. Both GABA and somatostatin hyperpolarized the edge cells but through different ionic mechanisms. GABA activated a chloride current while somatostatin activated a current most likely carried by potassium which, however, could not be blocked by any of the conventional potassium blockers.

Animals↗
PubMed1991

A new population of neurons with crossed axons in the lamprey spinal cord.

Neurons with contralateral, rostrally and caudally projecting axons were studied in whole mounts of lamprey spinal cord using retrograde labelling techniques with fluorescent dextran-amines, cobalt-lysine or horseradish peroxidase. A previously unknown large population (180-300 cells per hemisegment) of small (less than 25 microns) cells with contralateral projecting axons is described. Their axons extend over less than 5 segments rostrally or caudally. The number of these cells per segment was relatively constant in the rostral half of the spinal cord, but increased significantly in the caudal half. In comparison, medium-sized cells with contralateral axons corresponding to previously identified premotor interneurons were far less numerous (14-21 per hemisegment) and their axons extended more than 5 segments. Contralaterally projecting edge cells (intraspinal stretch receptor neurons) with principal rostral or caudal axons plus short collaterals in the other direction were distributed throughout the length of the spinal cord, whereas large and giant cells with a varied morphology were found in the caudal half.

Animals↗
PubMed1991

5-Hydroxytryptamine depresses reticulospinal excitatory postsynaptic potentials in motoneurons of the lamprey.

Application of 5-hydroxytryptamine (5-HT) to the lamprey spinal cord in vitro reversibly depressed the chemical component of excitatory post-synaptic potentials recorded intracellularly in motoneurons and evoked by stimulation of single reticulospinal Müller cells. The depression could be produced either by local application of small volumes of 10 mM 5-HT to the surface of the spinal cord or by bath-application of 1 or 10 microM 5-HT. No effect on the input resistance of the postsynaptic cells or their sensitivity to glutamate, the suspected transmitter at this synapse, could be detected, suggesting the possibility of a presynaptic action of 5-HT at this synapse in the lamprey.

2-Amino-5-phosphonovalerate↗
PubMed1991

Putative GABAergic input to axons of spinal interneurons and primary sensory neurons in the lamprey spinal cord as shown by intracellular Lucifer yellow and GABA immunohistochemistry.

GABAergic phasic modulation of the membrane potential occurs in spinal interneurons during fictive locomotion in lamprey presumably indicating a presynaptic inhibition. GABA also modulates synaptic transmission from primary sensory neurons (dorsal cells) at a presynaptic site. From these findings GABA terminals would be expected to be in close contact with phasically modulated axons of spinal interneurons and/or dorsal cells and their axons. To test this supposition intracellular injections of Lucifer yellow into spinal interneurons or dorsal cells were combined with GABA immunohistochemistry. GABA-immunoreactive (ir) varicosities were found to be in close contact (less than 1 micron distance) with axons modulated during fictive locomotion as well as dorsal cell axons. Small GABA-ir bipolar neurons form processes, which are in close contact with the axons of dorsal cells.

Animals↗
PubMed1991

A computer based model for realistic simulations of neural networks. I. The single neuron and synaptic interaction.

The use of computer simulations as a neurophysiological tool creates new possibilities to understand complex systems and to test whether a given model can explain experimental findings. Simulations, however, require a detailed specification of the model, including the nerve cell action potential and synaptic transmission. We describe a neuron model of intermediate complexity, with a small number of compartments representing the soma and the dendritic tree, and equipped with Na+, K+, Ca2+, and Ca2+ dependent K+ channels. Conductance changes in the different compartments are used to model conventional excitatory and inhibitory synaptic interactions. Voltage dependent NMDA-receptor channels are also included, and influence both the electrical conductance and the inflow of Ca2+ ions. This neuron model has been designed for the analysis of neural networks and specifically for the simulation of the network generating locomotion in a simple vertebrate, the lamprey. By assigning experimentally established properties to the simulated cells and their synapses, it has been possible to verify the sufficiency of these properties to account for a number of experimental findings of the network in operation. The model is, however, sufficiently general to be useful for realistic simulation also of other neural systems.

Computer Simulation↗
PubMed1991

A calcium-channel antagonist can prevent paramyxovirus-induced neurodegeneration.

Mumps virus caused a partially lytic infection in cultivated rat embryonic dorsal root ganglion neurons with a restricted formation of viral components. The neuronal degeneration was markedly enhanced by increasing the calcium concentration of the medium and could be almost totally inhibited by the dihydropyridine calcium channel antagonist nifedipine. The drug had no effect on a productive and completely lytic Sendai virus infection of the neurons. A previous neurophysiological study has shown that a reduced calcium influx occurs during the action potential early during the infection. The present study suggests a crucial role of calcium in neurodegeneration induced by certain viruses.

Animals↗
PubMed1991

Computer simulations of N-methyl-D-aspartate receptor-induced membrane properties in a neuron model.

1. To evaluate the role of N-methyl-D-aspartate (NMDA) receptors in simulations of the lamprey spinal locomotor network, we developed a computer-simulated electrical model of a neuron that contains NMDA channels in addition to voltage-gated Na+, K+, and Ca2+ channels and Ca(2+)-activated K+ channels [K(Ca) channels]. 2. The voltage dependence of the Mg2+ block of the Na(+)-K+ current flow through the NMDA channel was modeled according to a scheme of open-channel block. To account for the regulation of K(Ca) channels by NMDA and membrane voltage, we modeled two separate Ca2+ pools that had different voltage dependencies and dynamics. 3. Pacemaker-like membrane potential oscillations could be elicited in the model neuron, which resembled those observed experimentally in the presence of bath-applied NMDA and tetrodotoxin. The effect of changing different channel parameters were tested to determine under which conditions such membrane potential oscillations could occur. 4. The oscillation amplitude was determined by the potential levels at which the NMDA channels and voltage-dependent K+ channels, respectively, were activated. The oscillation frequency and the relative durations of the de- and hyperpolarized phases of the oscillations were determined by the balance between the depolarizing (NMDA channels) and hyperpolarizing [K(Ca) channels] currents. 5. Simulated alterations of the Mg2+ concentration and the K+ conductance as well as injection of constant current caused changes of the oscillations corresponding to those observed experimentally. The de- and hyperpolarizing phases could be reset by brief current pulses. 6. We conclude that the present model can account for the effects of bath-applied NMDA on spinal neurons. This permits an incorporation of NMDA-receptor-mediated properties in simulation models of the lamprey locomotor network.

Action Potentials↗
PubMed1991

Primary afferents evoke excitatory amino acid receptor-mediated EPSPs that are modulated by presynaptic GABAB receptors in lamprey.

1. The primary afferent neurons (dorsal cells) are of two types in lamprey, which are fast (touch) and slowly adapting (pressure), respectively. Intracellular stimulation of such sensory neurons evokes mono- and polysynaptic excitatory postsynaptic potentials (EPSPs) in spinobulbar neurons (giant interneurons) and in unidentified interneurons. Paired intracellular recordings between identified sensory cells and spinobulbar neurons made it possible to study the synaptic transmission in detail. It is shown that both touch and pressure primary afferents utilize excitatory amino acid (EAA) transmission and, furthermore, that these effects are subject to a presynaptic GABAB receptor modulation. 2. The monosynaptic mixed electrical and chemical EPSPs in giant interneurons had a mean peak amplitude of 3.2 +/- 1.3 (SD) mV, a time to peak of 4.7 +/- 1.2 ms, and a duration at one-half peak amplitude of 9.4 +/- 3.2 ms. Corresponding results were obtained with dorsal root or dorsal column stimulation. Seventy percent of the fast-adapting dorsal cells of the "touch" type evoked monosynaptic mixed EPSPs in giant interneurons, whereas only 3% of the slowly adapting "pressure" dorsal cells did. 3. The chemical part of the monosynaptic EPSPs evoked in giant interneurons was, in all cases tested, blocked by application of EAA antagonists, like the nonselective antagonist kynurenic acid (KYAC; 2 mM). The selective kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM) had a similar effect, whereas the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-aminophosphono-5-valeric acid (AP-5; 200-400 microM) did not change the EPSP, even in the absence of magnesium ions. 4. The monosynaptic excitatory synaptic transmission was modulated by application of the selective GABAB receptor agonist L-baclofen (5-10 mM local droplet application or 100-1,000 microM bath applied) or by gamma-aminobutyric acid (GABA; 100-1,000 microM), also when GABAA receptor-evoked effects were blocked by bicuculline (10 microM). L-baclofen or GABA in combination with bicuculline did not evoke any effects in the postsynaptic neuron on membrane potential, input resistance, or spike threshold. Therefore the effects of the GABAB receptor activation most likely occurs at the presynaptic afferent level. 5. In conclusion, the monosynaptic excitation from skin mechanoreceptors evoked in spinobulbar neurons is mediated by EAA receptors of the kainate/AMPA type. GABAB receptor activation causes a depression of this EPSP, most likely because of a presynaptic action. GABA interneurons are known to form close appositions on sensory axons in the lamprey.

2-Amino-5-phosphonovalerate↗
PubMed1991

The involvement of GABAB receptors and coupled G-proteins in spinal GABAergic presynaptic inhibition.

GABA acts as a presynaptic inhibitory transmitter in the spinal cord. In the lamprey, it has recently been shown that it acts in this way at both primary sensory and motor system synapses and is important in the generation of a locomotor rhythm. Both GABAA and GABAB receptors are activated at these sites by GABA released during physiological activity. In some systems, GABAB receptor activation has been shown to lead to modulation of ion channel function indirectly through the action of a pertussis toxin (PTX)-sensitive G-protein. Here we have studied the mechanism of action of the presynaptic GABAB receptor in this system. GABAB receptor activation leads to a decrease in axonal membrane impedance and also to a reduction in the axonal action potential duration. The ionic basis for this response remains unknown, though it is not, unlike the response to GABAA receptor activation, mediated by an increase in conductance to Cl-. The effects of GABAB receptor antagonism with phaclofen are mimicked by pretreatment of the spinal cord with PTX. Because this procedure inactivates certain classes of G-proteins, it seemed likely that the GABAB receptor-mediated effects are initiated via a presynaptic population of PTX-sensitive G-proteins. Experiments in which only presynaptic G-proteins were interfered with indicate that this is so. Stable analogs of GTP and GDP were used to activate permanently or to antagonize, respectively, the GTP binding site in the presynaptic component of these spinal synapses. We conclude that GABAB receptor-mediated synaptic suppression in the spinal cord is caused by GTP binding to presynaptic G-proteins linked to the GABAB receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Synaptic effects of intraspinal stretch receptor neurons mediating movement-related feedback during locomotion.

The flattened lamprey spinal cord contains stretch-sensitive edge cells located along the lateral margin, with dendritic processes sensing the lateral bending of the cord during each swim cycle. These intraspinal stretch receptor neurons provide movement-related sensory feedback input to the generator network for locomotion causing a powerful entrainment of the rhythm. In order to elucidate the synaptic effects of edge cells we have performed paired intracellular recordings and staining with Lucifer yellow. Monosynaptic connections that may explain entrainment were found to locomotor central pattern generator interneurons. Edge cells with an ipsilateral axon elicited excitatory postsynaptic potentials (EPSPs) in ipsilateral interneurons. In addition, such edge cells evoked kainate/quisqualate receptor mediated EPSPs in ipsilateral motoneurons. This pathway mediates an intraspinal stretch reflex analogous to the muscle spindle mediated stretch reflex of mammals. Edge cells with a contralateral axon produced monosynaptic glycinergic IPSPs in contralateral neurons, including contralateral edge cells.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1990

Neuropeptide Y-immunoreactive spinal neurons make close appositions on axons of primary sensory afferents.

The dorsal cells in the lamprey are primary sensory neurons located in a parasagittal region of the spinal cord. In the same plane neuropeptide Y (NPY) immunoreactivity has been described. To investigate if the dorsal cells were in contact with NPY-immunoreactive (ir) fibers and cell bodies, intracellular injections of Lucifer yellow into identified dorsal cells were combined with NPY immunohistochemistry. NPY-ir varicosities were found to be in close apposition to both the descending and the ascending axon of dorsal cells. No NPY-ir boutons were seen in close contact with the dorsal cell bodies.

Afferent Pathways↗