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Resetting intrinsic purinergic modulation of neural activity: an associative mechanism?
Dale N
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The purines, ATP and adenosine, control the rundown and termination of swimming in the Xenopus embryo. This intrinsic purinergic modulation, unavoidably present during every swimming episode, could lead to stereotyped inflexible behavior and consequently could jeopardize the survival of the embryo. To explore whether this control system can exhibit adaptability, I have used a minimal simulation in which a model neuron released ATP that (1) inhibited K+ currents and (2) was converted by ectonucleotidases to adenosine, which then inhibited Ca2+ currents. The model neuron exhibited an accommodating spike train controlled by the actions of ATP and adenosine. Feedforward inhibition by the upstream metabolite ADP of the ecto-5'-nucleotidase that converts AMP to adenosine introduced adaptability and allowed the resetting of spike accommodation. The strength of feedforward inhibition determined the extent to which resetting could occur. I have tested these predictions by examining swimming in the real embryo. The rundown of swimming was reset in a manner similar to that predicted by the single-neuron model. By blocking the purinoceptors, I have demonstrated that resetting in the embryo is attributable to the actions of the purines and results from feedforward inhibition of adenosine production. The resetting of rundown in the motor systems can be reformulated as an associative mechanism in which the temporal coincidence of two stimuli can prolong network activity if they fall within a particular time window. The length of the time window and the magnitude of the prolongation of neural activity both depend on the strength of the feedforward ADP-mediated inhibition of the ecto-5'-nucleotidase.
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