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Low-voltage-activated calcium channels in the lamprey locomotor network: Simulation and experiment
KTH, Superseded Departments, Numerical Analysis and Computer Science, NADA.ORCID iD: 0000-0002-0550-0739
KTH, Superseded Departments, Numerical Analysis and Computer Science, NADA.ORCID iD: 0000-0002-2358-7815
1997 (English)In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 77, no 4, 1795-1812 p.Article in journal (Refereed) Published
Abstract [en]

To evaluate the role of low-voltage-activated (LVA) calcium channels in the lamprey spinal locomotor network, a previous computer simulation model has been extended to include LVA calcium channels. It is also of interest to explore the consequences of a LVA conductance for the electrical behavior of the single neuron. The LVA calcium channel was modeled with voltage-dependent activation and inactivation using the m(3)h form, following a Hodgkin-Huxley paradigm. Experimental data from lamprey neurons was used to provide parameter values of the single cell model. The presence of a LVA calcium conductance in the model could account for the occurrence of a rebound depolarization in the simulation model. The influence of holding potential on the occurrence of a rebound as well the latency at which it is elicited was investigated and compared with previous experiments. The probability of a rebound increased at a more depolarized holding potential and the latency was also reduced under these conditions. Furthermore, the effect of changing the holding potential and the reversal potential of the calcium dependent potassium conductance were tested to determine under which conditions several rebound spikes could be elicited after a single inhibitory pulse in the simulation model. A reduction of the slow afterhyperpolarization (sAHP) after the action potential reduced the tendency for a train of rebound spikes. The experimental effects of gamma-aminobutyric acid-B (GABA(B)) receptor activation were simulated by reducing the maximal LVA calcium conductance. A reduced tendency for rebound firing and a slower rising phase with sinusoidal current stimulation was observed, in accordance with earlier experiments. The effect of reducing the slow afterhyperpolarization and reducing the LVA calcium current was tested experimentally in the lamprey spinal cord, during N-methyl-D-aspartate (NMDA)-induced fictive locomotion. The reduction of burst frequency was more pronounced with GABA(B) agonists than with apamin (inhibitor of K-(Ca) current) when using high NMDA concentration (high burst frequency). The burst frequency increased after the addition of a LVA calcium current to the simulated segmental network, due to a faster recovery during the inhibitory phase as the activity switches between the sides. This result is consistent with earlier experimental findings because GABA(B) receptor agonists reduce the locomotor frequency. These results taken together suggest that the LVA calcium chancels contribute to a larger degree with respect to the burst frequency regulation than the sAHP mechanism at higher burst frequencies. The range in which a regular burst pattern can be simulated is extended in the lower range by the addition of LVA calcium channels, which leads to more stable activity at low locomotor frequencies. We conclude that the present model can account for rebound firing and trains of rebound spikes in lamprey neurons. The effects of GABA(B) receptor activation on the network level is consistent with a reduction of the calcium current through LVA calcium channels even though GABA(B) receptor activation will affect the sAHP indirectly and also presynaptic inhibition.

Place, publisher, year, edition, pages
1997. Vol. 77, no 4, 1795-1812 p.
Keyword [en]
THALAMOCORTICAL RELAY NEURONS, ELICITS FICTIVE LOCOMOTION, COMPUTER-BASED MODEL, SPINAL-CORD INVITRO, MEMBRANE-PROPERTIES, NEURAL NETWORKS, THALAMIC RELAY, INTERSEGMENTAL COORDINATION, REALISTIC SIMULATIONS, SYNAPTIC-INTERACTIONS
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:kth:diva-13357ISI: A1997WU25200010OAI: oai:DiVA.org:kth-13357DiVA: diva2:324213
Note
QC 20100614Available from: 2010-06-14 Created: 2010-06-14 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Modeling of bursting mechanisms and coordination in a spinal central pattern generator
Open this publication in new window or tab >>Modeling of bursting mechanisms and coordination in a spinal central pattern generator
1998 (English)Doctoral thesis, comprehensive summary (Other scientific)
Abstract [en]

Mechanisms underlying lotal bursting as well as coordinationbetween different levels of a spinal CPG generating locomotionhave been investigated using computer simulations. A"primitive" jawless vertebrate, the lamprey, is used a.s aprototype model. Most simulations have been conducted using abiophysical neu ron model built on the Hodgkin-Huxley formalismand equipped with Nu+, K+,Ca²+, Kca, LVACa²+ and NMDA activated channels. Inhibitory andexcitatory AMPA/kainate and NMDA synapses are modeled as timedependent conductances with appropriate reversal potentials.For tomparison, Morris-Letar oscillators as well as adaptingleaky integrator-like units are also used.

The basic identified building blocks of the CPG, generatingalternating left right burst activity, tonsist of ipsilaterallyprojecting excitatory neurons (E) and contralaterallyprojecting inhibitory neurons (C). The model neurons are connected in the same way ss has been established experimentally.Sinte several complementary mechanisms may play a role, thepotential of two different neural mechanisms have been exploredwhich can provide burst activity at the segmen tal level, andintersegmental coordination. When alternating left-rightactivity is produced through an escape-like mechanism the quietside is able to become ac tive despite ongoing inhibition fromthe contralateral side. Reciprocal inhibition is then a crucialburst terminating factor. Burst frequency is strongly affectedby the effective inhibition and the drive to escape fromongoing inhibition. Several factors influence this process. Kcacurrents control spike frequency on the active sideand also a post-burst hyperpolarization on the inactive side.Postin hibitory rebound properties, carried by e.g. low voltageactivatedCa²+ currents further can promote escape. Phasicipsilateral excitation and NMDA membrane properties stabilizethe rhythm, especially in the lower frequency range. Severalexperimental observations can be explained based on the effectthese different factors have on effective inhibition andtendency for escape.

Bursting can, however, also be produced by a networkdeprived of inhibition, showing that powerful burst terminatingmechanisms not requiring inhibition exist. In the model withbiophysically detailed neurons such a mechanism could beactivation ofKcacurrents due to accumulation ofCa²+ during the active phase. As shown innon-spiking, as well as biophysically detailed models, aconstant burst proportion over a wide frequency range can beachieved by modulation of the rel ative strength of adaptationin such networks. The left-right inhibition causes left-rightalternation but may not affect the frequency of bursting.

When both types of lotal oscillatory networks are extendedlongitudinally, a rostral to caudal phase delay is producedwhen caudal projections are extended further than the rostralenes. However, the excitatory versus inhibitory projec tionsmay have different roles in the two alternative models. Thisrelative phase delay expressed as % of cycle duration,increases in general with frequency. The simulations suggestthat the conditions at the ends of the simulated chain arecritical for the resulting phase lag. The capability ofbuffering against frequency variations and rapid adjustmentsfollowing perturbations is discussed and com pared with chainsof relaxation oscillators and phase-coupled oscillators.

Place, publisher, year, edition, pages
Stockholm: KTH, 1998. 82 p.
Series
Trita-NA, ISSN 0348-2952 ; 98:10
Keyword
adaptation, central pattern generator, computer simulation, inter segmental coordination, lamprey, locomotion, neural network, rhythmogenesis
National Category
Engineering and Technology
Identifiers
urn:nbn:se:kth:diva-2673 (URN)91-7170-255-5 (ISBN)
Public defence
1998-06-16, 00:00
Note
QC 20100616Available from: 2000-01-01 Created: 2000-01-01 Last updated: 2010-06-16Bibliographically approved

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