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Riluzole-induced oscillations in spinal networks

We previously showed in dissociated cultures of fetal rat spinal cord that disinhibition-induced bursting is based on intrinsic spiking, network recruitment, and a network refractory period after the bursts. A persistent sodium current (I(NaP)) underlies intrinsic spiking, which, by recurrent excitation, generates the bursting activity. Although full blockade of I(NaP) with riluzole disrupts such bursting, the present study shows that partial blockade of I(NaP) with low doses of riluzole maintains bursting activity with unchanged burst rate and burst duration. More important, low doses of riluzole turned bursts composed of persistent activity into bursts composed of oscillatory activity at around 5 Hz. In a search for the mechanisms underlying the generation of such intraburst oscillations, we found that activity-dependent synaptic depression was not changed with low doses of riluzole. On the other hand, low doses of riluzole strongly increased spike-frequency adaptation and led to early depolarization block when bursts were simulated by injecting long current pulses into single neurons in the absence of fast synaptic transmission. Phenytoin is another I(NaP) blocker. When applied in doses that reduced intrinsic activity by 80-90%, as did low doses of riluzole, it had no effect either on spike-frequency adaptation or on depolarization block. Nor did phenytoin induce intraburst oscillations after disinhibition. A theoretical model incorporating a depolarization block mechanism could reproduce the generation of intraburst oscillations at the network level. From these findings we conclude that riluzole-induced intraburst oscillations are a network-driven phenomenon whose major accommodation mechanism is depolarization block arising from strong sodium channel inactivation

Keywords : Action Potentials,Animals,Bicuculline,Cells,Cultured,cytology,drug effects,Electric Stimulation,Embryo,Mammalian,Excitatory Amino Acid Antagonists,GABA Antagonists,Ganglia,Spinal,Hand,In Vitro Techniques,Inhibitory Postsynaptic Potentials,methods,Nerve Net,Neural Inhibition,Neurons,Patch-Clamp Techniques,Periodicity,pharmacology,physiology,radiation effects,Rats,Riluzole,Sodium,Spinal Cord,Switzerland,Synaptic Transmission,transmission,, Oscillations,Spinal,Networks, different types of physiotherapy

Date of Publication : 2007 May

Authors : Yvon C;Czarnecki A;Streit J;

Organisation : Department of Physiology, University of Bern, Switzerland. [email protected]

Journal of Publication : J Neurophysiol

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/17344372

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