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An increased N-methyl-D-aspartate receptor conductance is associated with intrinsic bursting behavior

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Background

Seizure activity is often accompanied by an increase in the number of intrinsically bursting neurons [1]. The N-methyl-D-aspartate (NMDA) receptor, a channel known to be involved in many seizure models, represents one mechanism by which intrinsic bursting may arise, since 30–50% of these channels are bound at ambient concentrations of glutamate. In adult rat, intrinsic bursting has been induced in pyramidal neurons of the prefrontal cortex (PFC) through a combination of NMDA and dopamine type 1 (D1) receptor agonist [2]. Here we used the in vitro mouse neocortex and a computational model to further investigate the basis for bursting in the context of epileptiform activity.

Results

In mouse frontal cortex, application of 8–10 μM NMDA and 2–5 μM D1 agonist SKF 38393 elicited intrinsic bursting in ~50% of pyramidal neurons. A computational pyramidal neuron model consisting of five compartments with the sodium, potassium, calcium-activated potassium and NMDA channels was used to investigate the conditions necessary for bursting. In this model D1 agonist caused an amplification of the NMDA current. Our simulations indicate that increasing the NMDA receptor conductance transformed a regularly spiking neuron into a burster (see fig. 1). Interestingly, the bursting behavior appeared only when both NMDA receptor and calcium-activated potassium conductance were included.

Figure 1
figure1

Experimental and Model Neuron Firing Behaviour.

Conclusion

The NMDA receptor is associated with production of intrinsic bursting behavior in mouse cortical pyramidal neurons, and, together with a calcium-activated K conductance, is sufficient to cause spontaneous bursting in a computational model of pyramidal neuron. These and previous results indicate that the NMDA receptor has the potential to drive the bursting behavior that characterizes seizures.

References

  1. 1.

    Topolnik L, Steriade M, Timofeev I: Hyperexcitability of intact neurons underlies acute development of trauma-related electrographic seizures in cats in vivo. Eur J Neurosci. 2003, 18: 486-96. 10.1046/j.1460-9568.2003.02742.x.

  2. 2.

    Durstewitz D, Gabriel T: Dynamical Basis of Irregular Spiking in NMDA-Driven Prefrontal Cortex Neurons. Cerebral Cortex. 2006 in press.

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Acknowledgements

This work was supported in part by the Falk Foundation and the Linn family.

Author information

Correspondence to Amber Martell.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Martell, A., Marler, S., Lee, H.C. et al. An increased N-methyl-D-aspartate receptor conductance is associated with intrinsic bursting behavior. BMC Neurosci 8, P144 (2007) doi:10.1186/1471-2202-8-S2-P144

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Keywords

  • NMDA Receptor
  • Pyramidal Neuron
  • Epileptiform Activity
  • Potassium Conductance
  • NMDA Channel