Search PubMed⌕ Search

Biomedical subjects

A Lansner

Publications and source records attributed to A Lansner.

26 records · Page 2Linked to original sources
PubMed1992

Computer simulation of the segmental neural network generating locomotion in lamprey by using populations of network interneurons.

Realistic computer simulations of the experimentally established local spinal cord neural network generating swimming in the lamprey have been performed. Populations of network interneurons were used in which cellular properties, like cell size and membrane conductance including voltage dependent ion channels were randomly distributed around experimentally obtained mean values, as were synaptic conductances (kainate/AMPA, NMDA, glycine) and delays. This population model displayed more robust burst activity over a wider frequency range than the more simple subsample model used previously, and the pattern of interneuronal activity was appropriate. The strength of the reciprocal inhibition played a very important role in the regulation of burst frequency, and just by changing the inhibitory bias the entire physiological range could be covered. At the lower frequency range of bursting the segmental excitatory interneurons provide stability as does the activation of voltage dependent NMDA receptors. Spike frequency adaptation by means of summation of afterhyperpolarization (AHP) serves as a major burst terminating factor, and at lower rates the membrane properties conferred by the NMDA receptor activation. The lateral interneurons were not of critical importance for the burst termination. They may, however, be of particular importance for inducing a rapid burst termination during for instance steering and righting reactions. Several cellular factors combine to provide a secure and stable motor pattern in the entire frequency range.

Animals↗
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

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

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↗
PubMed1989

Mechanisms underlying the serotonergic modulation of the spinal circuitry for locomotion in lamprey.

The central nervous system of the lamprey contains serotonergic (5-hydroxytryptamine, 5-HT) neurones both in the spinal cord and in the brainstem. Endogenously released 5-HT from these systems modulates the pattern of fictive locomotion induced in the in vitro preparation; the burst rate is lowered and burst discharges become longer and of higher intensity. Local application of 5-HT, mimicking activation of the 5-HT systems, has a specific effect on the late phase of the afterhyperpolarization (AHP) in motoneurones and interneurones. 5-HT markedly reduces the amplitude of the late AHP without affecting passive membrane properties or the shape or threshold of the action potential. This 5-HT effect appears to result from a direct action on the calcium-dependent potassium channels underlying the late phase of the AHP. A reduction of the amplitude of the AHP will result in altered spike discharge characteristics, with potentiation of the response (discharge rate) to a given excitatory input in all neurones influenced by 5-HT. It is suggested that the modulatory effect of 5-HT on fictive locomotion can be attributed to its action on the late AHP and thereby to the potentiation of excitability in excitatory and inhibitory interneurones in the generator circuitry. This has been further corroborated in computer simulation studies of a network model, where the action of 5-HT was simulated by decreasing AHP amplitude, resulting in a slowing of the rhythm analogous to the effect demonstrated experimentally.

Animals↗
PubMed1988

Simulation of the segmental burst generating network for locomotion in lamprey.

Recently a segmental network of inhibitory and excitatory interneurones, which are active during locomotion, has been described in the lamprey, a lower vertebrate. The interactions between the different neurones were established by paired intracellular recordings. A computer simulation of the segmental network has been performed, which shows that with the established neuronal connectivity rhythmic alternating burst activity can be generated within the upper part of the normal physiological range of locomotion. Three neurones of each kind were used (altogether 18 neurones). As shown previously the lower frequency range used in locomotion most likely depends on an activation of voltage-dependent N-methyl-D-aspartate (NMDA) receptors, which could, however, not be simulated with the present neuronal models.

Animals↗
PubMedDate not supplied

Modeling of substance P and 5-HT induced synaptic plasticity in the lamprey spinal CPG: consequences for network pattern generation.

Consequences of synaptic plasticity in the lamprey spinal CPG are analyzed by means of simulations. This is motivated by the effects substance P (a tachykinin) and serotonin (5-hydroxytryptamin; 5-HT) have on synaptic transmission in the locomotor network. Activity-dependent synaptic depression and potentiation have recently been shown experimentally using paired intracellular recordings. Although normally activity-dependent plasticity presumably does not contribute to the patterning of network activity, this changes in the presence of the neuromodulators substance P and 5-HT, which evoke significant plasticity. Substance P can induce a faster and larger depression of inhibitory connections but potentiation of excitatory inputs, whereas 5-HT induces facilitation of both inhibitory and excitatory inputs. Changes in the amplitude of the first postsynaptic potential are also seen. These changes could thus be a potential mechanism underlying the modulatory role these substances have on the rhythmic network activity. The aim of the present study has been to implement the activity dependent synaptic depression and facilitation induced by substance P and 5-HT into two alternative models of the lamprey spinal locomotor network, one relying on reciprocal inhibition for bursting and one in which each hemicord is capable of oscillations. The consequences of the plasticity of inhibitory and excitatory connections are then explored on the network level. In the intact spinal cord, tachykinins and 5-HT, which can be endogenously released, increase and decrease the frequency of the alternating left-right burst pattern, respectively. The frequency decreasing effect of 5-HT has previously been explained based on its conductance decreasing effect on K(Ca) underlying the postspike afterhyperpolarization (AHP). The present simulations show that short-term synaptic plasticity may have strong effects on frequency regulation in the lamprey spinal CPG. In the network model relying on reciprocal inhibition, the observed effects substance P and 5-HT have on network behavior (i.e., a frequency increase and decrease respectively) can to a substantial part be explained by their effects on the total extent and time dynamics of synaptic depression and facilitation. The cellular effects of these substances will in the 5-HT case further contribute to its network effect.

Action Potentials↗