Aug 14, 2015

Synergy of AMPA and NMDA receptor currents in dopaminergic neurons: a modeling study

BioRxiv : the Preprint Server for Biology
Denis ZakharovAlexey Kuznetsov

Abstract

Dopaminergic (DA) neurons display two modes of firing: low-frequency tonic and high-frequency bursts. The high frequency firing within the bursts is attributed to NMDA, but not AMPA receptor activation. In our models of the DA neuron, both biophysical and abstract, the NMDA receptor current can significantly increase their firing frequency, whereas the AMPA receptor current is not able to evoke high-frequency activity and usually suppresses firing. However, both currents are produced by glutamate receptors and, consequently, are often co-activated. Here we consider combined influence of AMPA and NMDA synaptic input in the models of the DA neuron. Different types of neuronal activity (resting state, low frequency, or high frequency firing) are observed depending on the conductance of the AMPAR and NMDAR currents. In two models, biophysical and reduced, we show that the firing frequency increases more effectively if both receptors are co-activated for certain parameter values. In particular, in the more quantitative biophysical model, the maximal frequency is 40% greater than that with NMDAR alone. The dynamical mechanism of such frequency growth is explained in the framework of phase space evolution using the reduced model. In s...Continue Reading

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Mentioned in this Paper

Study
Tonics
GRIN1
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Neurons
Calcium Channel
N-Methylaspartate
Anatomical Space Structure
Biophysics
Synapses

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