Volume 14 Supplement 1

Abstracts from the Twenty Second Annual Computational Neuroscience Meeting: CNS*2013

Open Access

Dopamine-NMDA interactions and relevance to gamma band synchrony in schizophrenia

BMC Neuroscience201314(Suppl 1):P218

DOI: 10.1186/1471-2202-14-S1-P218

Published: 8 July 2013

An increasing body of behavioral and physiological evidence shows that cortical activity operates optimally within a limited range of dopamine (DA) transmission within a broader inverted-U shaped relationship [1]. However, the exact mechanism through which DA leads to such non-monotonic modulation of network activity needs further investigation. Our recent work suggests that DA's modulation of potassium currents in the fast-spiking interneurons could be a potential mechanism underlying this inverted-U relationship [2]. Here we propose that another potential mechanism could contribute in the form of interactions between DA D1 receptors and NMDA conductance in the cortex. This has been an area of interest for many reasons including its relevance to the etiology of schizophrenia with deficits in both NMDA-mediated glutamate and DA transmission. Studies examining the relationship between DA and NMDA conductance in the cortex revealed that DA D1 receptors enhance NMDA responses [35].

In the current study, we incorporated DA's modulation of NMDA conductance at a network level and analyzed whether DA's modulation of NMDA currents could lead to an inverted-U shaped relationship with cortical activity. With this motivation, we simulated a neural network with 200 excitatory and 40 inhibitory quadratic integrate-and-fire neurons coupled with biologically realistic probabilities. In the simulated network, the effects of DA were implemented through varying the NMDA conductances in various combinations of synaptic types including excitatory-excitatory and excitatory-inhibitory. The network synchronization was analyzed through examining gamma band power in the local field potential. Parametrically varying the NMDA conductance revealed an inverted-U shaped relationship, with lower gamma band power at both low and high conductance levels and optimal synchronization occurring at intermediate conductance levels. Our findings reveal that DA's modulation of NMDA currents at the single cell level gives rise to a non-monotonic relationship between cortical gamma band synchrony and DA levels. These results together with those of [2] suggest that DA's modulation of potassium currents as well as NMDA-mediated currents may be complementary or synergistic mechanisms that give rise to the inverted-U shaped pattern in cortical activity across dopamine levels.

Authors’ Affiliations

Center for the Neural Basis of Cognition, Carnegie Mellon University
Department of Mathematics, University of Pittsburgh
Department of Psychiatry, University of Pittsburgh


  1. Williams GV, Castner SA: Under the curve: critical issues for elucidating D1 receptor function in working memory. Neuroscience. 2006, 139 (1): 263-276. 10.1016/j.neuroscience.2005.09.028.View ArticlePubMedGoogle Scholar
  2. Kömek K, Ermentrout GB, Walker CP, Cho RY: Dopamine and gamma band synchrony in schizophrenia--insights from computational and empirical studies. Eur J Neurosci. 2012, 36: 2146-2155. 10.1111/j.1460-9568.2012.08071.x.PubMed CentralView ArticlePubMedGoogle Scholar
  3. Seamans JK, Durstewitz D, Christie BR, Stevens CF, Sejnowski TJ: Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons. PNAS. 2001, 98 (1): 301-306. 10.1073/pnas.98.1.301.PubMed CentralView ArticlePubMedGoogle Scholar
  4. Wang J, O'Donnell P: D(1) dopamine receptors potentiate NMDA-mediated excitability increase in layer V prefrontal cortical pyramidal neurons. Cereb Cortex. 2001, 11 (5): 452-462. 10.1093/cercor/11.5.452.View ArticlePubMedGoogle Scholar
  5. Chen G, Greengard P, Yan Z: Potentiation of NMDA receptor currents by dopamine D1 receptors in prefrontal cortex. PNAS. 2004, 101 (8): 2596-2600. 10.1073/pnas.0308618100.PubMed CentralView ArticlePubMedGoogle Scholar


© Kömek et al; licensee BioMed Central Ltd. 2013

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