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

Denis Zakharov, Christopher Lapish, Boris Gutkin, Alexey Kuznetsov
doi: https://doi.org/10.1101/024653
Denis Zakharov
1Nonlinear dynamics department, Institute of Applied Physics, RAS, Nizhny Novgorod, Russia
2Laboratory of Nonlinear Physics, Nizhny Novgorod State University, Nizhny Novgorod, Russia
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Christopher Lapish
3Department of Psychology, IUPUI, Indianapolis, USA
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Boris Gutkin
4Group of Neural Theory, ENS, Paris, France.
5Centre for Cognition and Decision Making, National Research University Higher School of Economics, Moscow, Russia
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Alexey Kuznetsov
6Department of Mathematical Sciences and Center for Mathematical Modeling and Computational Sciences, IUPUI, Indianapolis, USA
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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 short, both the AMPAR and NMDAR currents flatten the voltage nullcline, providing the frequency increase, whereas only NMDA prevents complete unfolding of the nullcline, providing robust firing. Thus, we confirm a major role of the NMDAR in generating high-frequency firing and conclude that AMPAR activation further significantly increases the frequency.

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Posted August 14, 2015.
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Synergy of AMPA and NMDA receptor currents in dopaminergic neurons: a modeling study
Denis Zakharov, Christopher Lapish, Boris Gutkin, Alexey Kuznetsov
bioRxiv 024653; doi: https://doi.org/10.1101/024653
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Synergy of AMPA and NMDA receptor currents in dopaminergic neurons: a modeling study
Denis Zakharov, Christopher Lapish, Boris Gutkin, Alexey Kuznetsov
bioRxiv 024653; doi: https://doi.org/10.1101/024653

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