Roles of Ionic Currents in Lamprey CPG Neurons: A Modeling Study

Abstract

Huss M, Lansner A, Wallén P, El Manira A, Grillner S, Kotaleski JH. Roles of ionic currents in lamprey CPG neurons: a modeling study. J Neurophysiol 97: 2696 -2711. First published February 7, 2007 doi:10.1152/jn.00528.2006. The spinal network underlying locomotion in the lamprey consists of a core network of glutamatergic and glycinergic interneurons, previously studied experimentally and through mathematical modeling. We present a new and more detailed computational model of lamprey locomotor network neurons, based primarily on detailed electrophysiological measurements and incorporating new experimental findings. The model uses a HodgkinHuxley-like formalism and consists of 86 membrane compartments containing 12 types of ion currents. One of the goals was to introduce a fast, transient potassium current (K t ) and two sodium-dependent potassium currents, one faster (K NaF ) and one slower (K NaS ), in the model. Not only has the model lent support to the interpretation of experimental results but it has also provided predictions for further experimental analysis of single-network neurons. For example, K t was shown to be one critical factor for controlling action potential duration. In addition, the model has proved helpful in investigating the possible influence of the slow afterhyperpolarization on repetitive firing during ongoing activation. In particular, the balance between the simulated slow sodium-dependent and calcium-dependent potassium currents has been explored, as well as the possible involvement of dendritic conductances. I N T R O D U C T I O NThe lamprey CNS has widely served as a model system of the neural basis of vertebrate locomotion. There are fewer neurons in the lamprey than in higher vertebrates and the motor activity underlying locomotion can be maintained in the isolated spinal cord for days . The core of the lamprey spinal central pattern generator (CPG) consists of ipsilaterally projecting glutamatergic neurons and contralaterally projecting glycinergic neurons (Buchanan et al. 1982(Buchanan et al. , 1987Grillner 2003). One tool for investigating the lamprey CPG, in addition to the experimental approach, has been extensive modeling at different levels of abstraction ). Both biophysical single-cell and network models of the lamprey spinal CPG were previously described (see, e.g., Ekeberg et al. 1991;Grillner et al. 1988;Hellgren et al. 1992; for more abstract types of models also see Buchanan 1992;McClellan and Hagevik 1997;Williams 1992). Different aspects of the local spinal network were previously simulated using Hodgkin-Huxley types of models, including its modulation by sensory feedback, activation by supraspinal structures, and coordination along the spinal cord Ekeberg et al. 1991; Hellgren et al. 1999a,b;Kozlov et al. 2001;Tegnér et al. 1998Tegnér et al. , 1999Tråvén et al. 1993;Ullström et al. 1998;Wadden et al. 1997;Wallén et al. 1992). Understanding such systems at the neuronal network level is very demanding because of the complexity of the dynamic interactions within an...

Gating of steering signals through phasic modulation of reticulospinal neurons during locomotion

“…In a previous full-scale model of the lamprey spinal locomotor system (7), we used biophysically realistic models of each type of neuron [compartmental model (26)] with a realistic number of cells. Using this network model as a basis (Materials and Methods), we now introduce phasic modulation of the reticulospinal neurons (from the spinal locomotor network) and explore the complementary effects that this addition introduces, in particular in relation to the input from the optic tectum related to steering.…”

“…Biologically detailed lamprey spinal cell models (26) are used in large-scale simulations of the locomotor network (7) to replicate electric activity in command centers and the spinal cord. A mechanical model of swimming (27,28) is used for a quantitative evaluation of the locomotor response.…”

Simple cellular and network control principles govern complex patterns of motor behavior

“…Each excitatory (E) and inhibitory (I) neuron is modeled in a biophysically detailed manner (22) (see supporting information (SI) Movie S1, Movie S2, and Movie S3). Populations of 6,000 E and 4,000 I cells are simulated by using an 86-compartmental neuronal model (22,23) and a total of 760,000 synapses. The synapses and model neurons have properties that very closely resemble those of their biological counterparts, causing them to respond in the same way to synaptic input.…”

“…The synapses and model neurons have properties that very closely resemble those of their biological counterparts, causing them to respond in the same way to synaptic input. The different types of ion channels established experimentally are also modeled with voltage-dependent Na ϩ , subtypes of Ca 2ϩ , K ϩ channels and Na ϩ -and Ca 2ϩ -gated K ϩ channels (22). Cells are placed randomly within a space corresponding to the spinal cord (see Methods).…”

“…Populations of 6,000 E and 4,000 I cells were simulated by using an 86-compartment model with the different types of ion channels as established experimentally (22). The cell model is available from Model DB (accession code 93319): http://senselab.med.yale.edu/modeldb/.…”