Roles of Ionic Currents in Lamprey CPG Neurons: A Modeling Study (original) (raw)
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Role of A-current in lamprey locomotor network neurons
Neurocomputing, 2003
A compartmental model of lamprey central pattern generator neurons was built in order to examine the e ects of a fast, transient, high-voltage-activated potassium current (A-current) found experimentally. The model consisted of a soma, a compartment corresponding to the axon initial segment, and a dendritic tree. The simulation showed that the A-current was necessary for repetitive spiking in the single neuron following current injection. The functional role of adding an A-current was also examined in a network model. In this model, the A-current stabilizes the swimming rhythm by making the burst cycle duration and the number of spikes per burst less variable. All these e ects are also seen experimentally.
Low-voltage-activated calcium channels in the lamprey locomotor network: simulation and experiment
Journal of neurophysiology, 1997
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 m3h 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...
Ion channels of importance for the locomotor pattern generation in the lamprey brainstem-spinal cord
The Journal of Physiology, 2001
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.
Journal of computational neuroscience, 1998
It is crucial to determine the effects on the network level of a modulation of intrinsic membrane properties. The role calcium-dependent potassium channels, KCa, in the lamprey locomotor system has been investigated extensively. Earlier experimental studies have shown that apamin, which affects one type of KCa, increases the cycle duration of the locomotor network, due to effects on the burst termination. The effects of apamin were here larger when the network had a low level of activity (burst frequency 0.5 to 1 Hz) as compared to a higher rate (> 2 Hz). By using a previously developed simulation model based on the lamprey locomotor network, we show that the model could account for the frequency dependence of the apamin modulation, if only the KCa conductance activated by Ca2+ entering during the action potential was altered and not the KCa conductance activated by Ca2+ entering through NMDA channels. The present simulation model of the spinal network in the lamprey can thus acc...
Biological Cybernetics, 1992
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.
Ionic currents in identified swimmeret motor neurones of the crayfish Pacifastacus leniusculus
Journal of Experimental Biology, 1995
Ionic currents from freshly isolated and identified swimmeret motor neurones were characterized using a whole-cell patch-clamp technique. Two outward currents could be distinguished. A transient outward current was elicited by delivering depolarizing voltage steps from a holding potential of -80 mV. This current was inactivated by holding the cells at a potential of -40 mV and was also blocked completely by 4-aminopyridine. A second current had a sustained time course and continued to be activated at a holding potential of -40 mV. This current was partially blocked by tetraethylammonium. These outward currents resembled two previously described potassium currents: the K+ A-current and the delayed K+ rectifier current respectively. Two inward currents were also detected. A fast transient current was blocked by tetrodotoxin and inactivated at holding potential of -40 mV, suggesting that this is an inward Na+ current. A second inward current had a sustained time course and was affected...
Mathematical Analysis and Simulations of the Neural Circuit for Locomotion in Lampreys
Physical Review Letters, 2004
We analyze the dynamics of the neural circuit of the lamprey central pattern generator (CPG) This analysis provides insights into how neural interactions form oscillators and enable spontaneous oscillations in a network of damped oscillators, which were not apparent in previous simulations or abstract phase oscillator models. We also show how the different behaviour regimes (characterized by phase and amplitude relationships between oscillators) of forward/backward swimming, and turning, can be controlled using the neural connection strengths and external inputs.
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.
Ionic mechanisms of 3 types of functionally different neurons in the lamprey spinal cord
Brain Research, 1985
Action potentials and afterpotentials were compared in giant interneurons, sensory dorsal cells and large intraspinal axons in the lamprey spinal cord. Afterpotentials of giant interneurons and dorsal cells consisted of two hyperpolarizing phases, an early and a late one, which were separated by a delayed depolarization. The afterpotentials of axons had a single hyperpolarizing phase also followed by a delayed depolarization. Tetraethyl ammonium chloride (TEA+) eliminated the early phase of the afterhyperpolarization in giant interneurons, only partially reduced the early phase in dorsal cells and did not affect the single phase of axons. The delayed depolarization of dorsal cells was attenuated by TEA+ but in axons it was unaltered. The heavy metal ions Mn2+ and Co2+ (2 mM) eliminated the late phase in giant interneurons but did not reduce the late phase in dorsal cells. The delayed depolarization remained in both types of cell in the presence of these ions. Action potentials of giant interneurons and dorsal cells, but not those of axons, were broadened by TEA+. The TEA-prolonged action potentials were narrowed by Mn2+ applied in combination with TEA+. The afterhyperpolarizations of all 3 cells were reduced by injection of negative current and enhanced by positive current. Repetitive stimulation resulted in summation of the afterhyperpolarization in giant interneurons and dorsal cells. The results suggest that different sets of potassium channels are responsible for the afterhyperpolarizations in each type of cell. In giant interneurons fast channels which are sensitive to TEA+ may underlie the early phase and slow channels activated by calcium entry may underlie the slow phase. The early phase of dorsal cells may be caused by two types of fast channel, one similar to that in giant interneurons and another less sensitive to external TEA+. This latter type may also cause the afterhyperpolarization in axons. Although calcium channels appear to contribute to the action potentials of giant interneurons and dorsal cells, the late phase of the latter neurons does not seem to be activated by calcium entry. The delayed depolarizations of the neurons appear to be due to an inward current which is not carried by calcium.
Modeling of the Spinal Neuronal Circuitry Underlying Locomotion in a Lower Vertebratea
Annals of the New York Academy of Sciences, 1998
The neural circuitry generating lamprey undulatory swimming is among the most accessible and best known of the vertebrate neuronal locomotor systems. It therefore serves as an experimental model for such systems. Modeling and computer simulation of this system was initiated at a point when a significant part of the network had been identified, although much detail was still lacking. The model has been further developed over 10 years in close interaction with experiments. The local burst generating circuitry is formed by ipsilateral excitatory neurons and crossed reciprocal inhibitory neurons. Early models also incorporated an off-switch lateral interneuron (L), the connectivity of which suggested it could contribute to burst termination at moderate to high bursting frequencies. Later examination of this model suggested, however, that the L interneuron was not of primary importance for burst termination, and this was later verified experimentally. Further, early models explained the effects of 5-HT on bursting frequency, spike frequency, and burst duration as being due to its modulatory action on the spike frequency adaptation of lamprey premotor interneurons. In current network models, accumulated adaptation is in addition the main burst terminating factor. Drive-related modulation of adaptation is explored as a mechanism for control of burst duration. This produces an adequate burst frequency range and a constant burst proportion within each cycle. It further allows for hemisegmental bursting, which has been observed experimentally. The local burst generator forms the basis of a network model of the distributed pattern generator that extends along the spinal cord. Phase constancy and flexibility of intersegmental coordination has been studied in such a simulated network. Current modeling work focuses on neuromodulator circuitry and action, network responses to input transients, how to model the intact versus an isolated piece of spinal cord, as well as on improving an earlier neuromechanical model of lamprey swimming.