The Journal of Neuroscience, December 1, 2002, 22(23):10461-10469
Resetting Intrinsic Purinergic Modulation of Neural Activity: An
Associative Mechanism?
Nicholas
Dale
Department of Biological Sciences, University of Warwick, Coventry,
CV4 7AL, United Kingdom
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.
Key words:
ATP; adenosine; central pattern generator; ectonucleotidase; associative; purine
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